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Huang Z, Ji Y, Wang D, Guo N, Jin L, Zheng S, Liu Y, Shi H, Lin M, Zuo C. The Macular Pigment Optical Density (MPOD) Decrease in Chinese Primary Angle Closure Glaucoma Using the One-Wavelength Reflectometry Method. Curr Eye Res 2024; 49:1260-1268. [PMID: 39105271 DOI: 10.1080/02713683.2024.2381864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 05/17/2024] [Accepted: 07/01/2024] [Indexed: 08/07/2024]
Abstract
PURPOSE The objective of this study was to observe the macular pigment optical density (MPOD) and the relationship between MPOD and retinal thickness in Chinese primary angle-closure glaucoma (PACG) patients by the one-wavelength reflectometry method. METHODS This study was a prospective comparative observational study, including 39 eyes from 39 PACG patients (15 men and 24 women, mean age 61.89 ± 12.30) and 41 eyes from 41 controls (20 men and 21 women, mean age 63.24 ± 14.02). We measured the MPOD 7-degree area by the one-wavelength reflectometry method and analyzed both the max and mean optical density (OD). The central retinal thickness (CRT) and the total thickness of the macular ganglion cell layer (GCL), and inner plexiform layer (IPL)were measured by spectral-domain-optical coherence tomography (SD-OCT). Statistical methods such as Shapiro-Wilk test, Fisher's exact test, chi-square test, two independent samples test and Spearman's correlation coefficient were used to observe the differences in the MPOD between normal subjects and PACG patients and the correlation between the MPOD and retinal thickness. RESULTS The max optical density (Max OD) (PACG group: 0.302 ± 0.067d.u, control group: 0.372 ± 0.059d.u., p < .001) and mean optical density (Mean OD) (PACG group: 0.124 ± 0.035d.u., control group: 0.141 ± 0.028d.u., p < 0.05) were significantly reduced in PACG patients compared with control subjects. Significant decreases in GCL + IPL thickness (PACG group: 74.71 ± 39.56 μm, control group:113.61 ± 8.14 μm, p < 0.001) and CRT (PACG group: 254.49 ± 41.47 μm, control group:329.10 ± 18.57 μm, p < 0.001) were also observed in PACG eyes. There was no statistically significant correlation between the MPOD and GCL + IPL thickness (p = .639, p = .828). CONCLUSIONS MPOD was significantly lower in Chinese PACG patients than in the control group, potentially due to thinning of the GCL + IPL thickness. This study provides insights for the pathophysiology, assessment of PACG and potential guidance for lifestyle modifications.
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Affiliation(s)
- Zhihong Huang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Yuying Ji
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Dingqiao Wang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Ni Guo
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Ling Jin
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Shaoyang Zheng
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Yuan Liu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Huanyang Shi
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Mingkai Lin
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Chengguo Zuo
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
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Addo EK, Gorka JE, Allman SJ, Harrison DY, Sharifzadeh M, Hoffman RO, Hartnett ME, Varner MW, Bernstein PS. Ocular Effects of Prenatal Carotenoid Supplementation in the Mother and Her Child: The Lutein and Zeaxanthin in Pregnancy (L-ZIP) Randomized Trial - Report Number 2. OPHTHALMOLOGY SCIENCE 2024; 4:100537. [PMID: 39071916 PMCID: PMC11283155 DOI: 10.1016/j.xops.2024.100537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 03/21/2024] [Accepted: 04/16/2024] [Indexed: 07/30/2024]
Abstract
Purpose Lutein (L) and zeaxanthin (Z) are xanthophyll carotenoids that have been promoted to enhance maternal health and infant visual and neurodevelopment. In this study, we determined the effects of prenatal L and Z supplementation on systemic and ocular carotenoid status in the mother and her newborn infant (NCT03750968). This report focuses on the ocular effects of prenatal carotenoid supplementation. Design A prospective randomized clinical trial with 47 subjects randomly assigned by 1:1 allocation to receive standard-of-care prenatal vitamins along with 10 mg L and 2 mg Z softgel (Carotenoid Group) or standard-of-care prenatal vitamins with a placebo softgel (Control Group) starting in the first trimester. Subjects We enrolled low-risk pregnancy subjects aged ≥18 years from the obstetrics and gynecology clinic of the University of Utah Hospital. Methods Maternal macular, skin, and serum carotenoid concentrations were measured using autofluorescence imaging, resonance Raman spectroscopy, and high-performance liquid chromatography, respectively. Infants' ocular carotenoids and retinal architecture were measured by blue light reflectance imaging and spectral-domain OCT, respectively. Main Outcome Measures Changes in maternal and infant macular pigment, skin, and serum carotenoid status over the study period. Differences in infants' retinal maturity indicators between the 2 study groups. Results Following supplementation, there was a statistically significant increase in maternal macular pigment optical volume (P < 0.001) in the Carotenoid Group relative to the Control Group at all study time points, and there was no detectable maternal ocular carotenoid depletion. Infant skin and serum carotenoids increased significantly in the Carotenoid Group compared with the Control Group. As exploratory endpoints, infants in the Carotenoid Group had a 20% increase in macular pigment optical density (P = 0.242) and more mature foveal parameters compared with those in the Control Group. Conclusion Prenatal carotenoid supplementation significantly increased maternal and infant systemic carotenoids and caused a pattern of increased infant ocular carotenoid status, which may benefit both mothers and their infants' ocular development and function. This study provides important data to design and power a future multicenter study of prenatal carotenoid supplementation in higher-risk pregnancies. Financial Disclosures The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Affiliation(s)
- Emmanuel K. Addo
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, 65 Mario Capecchi Drive, Salt Lake City, Utah, 84132
- Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah
| | - Joanna E. Gorka
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, 65 Mario Capecchi Drive, Salt Lake City, Utah, 84132
| | - Susan J. Allman
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, 65 Mario Capecchi Drive, Salt Lake City, Utah, 84132
| | - Deborah Y. Harrison
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, 65 Mario Capecchi Drive, Salt Lake City, Utah, 84132
| | - Mohsen Sharifzadeh
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, 65 Mario Capecchi Drive, Salt Lake City, Utah, 84132
| | - Robert O. Hoffman
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, 65 Mario Capecchi Drive, Salt Lake City, Utah, 84132
| | - M. Elizabeth Hartnett
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, 65 Mario Capecchi Drive, Salt Lake City, Utah, 84132
| | - Michael W. Varner
- Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah
| | - Paul S. Bernstein
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, 65 Mario Capecchi Drive, Salt Lake City, Utah, 84132
- Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah
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Cozzi M, Casaluci M, Ruggi G, Airaldi M, Romano F, Bertoni A, Green-Gomez M, Nolan JM, Staurenghi G, Invernizzi A. In Vivo Correlation Between Macular Pigment Optical Volume and Retinal Layers Thickness. Invest Ophthalmol Vis Sci 2024; 65:23. [PMID: 39007849 PMCID: PMC467106 DOI: 10.1167/iovs.65.8.23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 06/27/2024] [Indexed: 07/16/2024] Open
Abstract
Purpose This study aims to investigate the potential in vivo relationship between macular pigment (MP) and retinal layers thickness in healthy subjects and dry, non-advanced age-related macular degeneration (AMD). Methods An observational, cross-sectional study was conducted. Healthy subjects >40 years and patients with early or intermediate AMD were recruited. Structural OCT and macular pigment optical volume (MPOV) were collected for each subject. Retinal layers parameters were calculated based on the standard early treatment diabetic retinopathy study (ETDRS) map. Additionally, MPOV within 1°, 2°, and 9° of eccentricity was assessed and associated with retinal layers thickness and volume. Linear mixed-effects models were used to test the relationship between MP and structural OCT parameters, while adjusting for known possible confounding factors. Results A total of 144 eyes of 91 subjects (60.4% females) were evaluated, comprising 43% normal eyes and 57% with early/intermediate AMD. Among the retinal layers, only the outer nuclear layer (ONL) thickness and volume appeared to be associated to higher MP levels. Specifically, the central ONL thickness was identified as a significant predictor of the MPOV 1°(P = 0.04), while the parafoveal ONL thickness (inner ETDRS subfield) was identified as a significant fixed effect on the MPOV 9° (P = 0.037). Age and the presence of drusen or subretinal drusenoid deposits were also tested without showing significant correlations. Conclusions Among the retinal layers examined, only the ONL thickness demonstrated a significant association with MPOV. Consequently, ONL thickness might serve as a potential biomarker related to MP levels.
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Affiliation(s)
- Mariano Cozzi
- Eye Clinic, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy
| | - Marco Casaluci
- Eye Clinic, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy
| | - Giada Ruggi
- Eye Clinic, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy
| | - Matteo Airaldi
- Eye Clinic, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy
| | - Francesco Romano
- Eye Clinic, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy
| | - Alice Bertoni
- Eye Clinic, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy
| | - Marina Green-Gomez
- Nutrition Research Centre Ireland, School of Health Science, Carriganore House, Waterford Institute of Technology, West Campus, Waterford, Ireland
| | - John M. Nolan
- Nutrition Research Centre Ireland, School of Health Science, Carriganore House, Waterford Institute of Technology, West Campus, Waterford, Ireland
| | - Giovanni Staurenghi
- Eye Clinic, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy
| | - Alessandro Invernizzi
- Eye Clinic, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy
- The University of Sydney, Save Sight Institute, Discipline of Ophthalmology, Sydney Medical School, Sydney, NSW, Australia
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Ahmadzadeh S, Ubeyitogullari A. Lutein encapsulation into dual-layered starch/zein gels using 3D food printing: Improved storage stability and in vitro bioaccessibility. Int J Biol Macromol 2024; 266:131305. [PMID: 38569990 DOI: 10.1016/j.ijbiomac.2024.131305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 03/23/2024] [Accepted: 03/30/2024] [Indexed: 04/05/2024]
Abstract
The ability of 3D printing to encapsulate, protect, and enhance lutein bioaccessibility was investigated under various printing conditions. A spiral-cube-shaped geometry was used to investigate the effects of printing parameters, namely zein concentration (Z; 20, 40, and 60 %) and printing speed (PS; 4, 8, 14, and 20 mm/s). Coaxial extrusion 3D printing was used with lutein-loaded zein as the internal flow material, and corn starch paste as the external flow material. The viscosities of the inks, microstructural properties, storage stability, and bioaccessibility of encapsulated lutein were determined. The sample printed with a zein concentration of 40 % at a printing speed of 14 mm/s (Z-40/PS-14) exhibited the best shape integrity. When lutein was entrapped in starch/zein gels (Z-40/PS-14), only 39 % of lutein degraded after 21 days at 25 °C, whereas 78 % degraded at the same time when crude lutein was studied. Similar improvements were also observed after storing at 50 °C for 21 days. Furthermore, after simulated digestion, the bioaccessibility of encapsulated lutein (9.8 %) was substantially higher than that of crude lutein (1.5 %). As a result, the developed delivery system using 3D printing could be an effective strategy for enhancing the chemical stability and bioaccessibility of bioactive compounds (BCs).
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Affiliation(s)
- Safoura Ahmadzadeh
- Department of Food Science, University of Arkansas, Fayetteville, AR 72704, USA
| | - Ali Ubeyitogullari
- Department of Food Science, University of Arkansas, Fayetteville, AR 72704, USA; Department of Biological and Agricultural Engineering, University of Arkansas, Fayetteville, AR 72701, USA.
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Rajs P, Liehneova I, Stranak Z. Macular pigment evaluation using dual-wavelength fundus auto-fluorescence imaging. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2024. [PMID: 38214110 DOI: 10.5507/bp.2023.051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2024] Open
Abstract
INTRODUCTION Macular pigment plays an important role in the reduction of oxidative stress and in preventing retinal diseases. Quick and easy measurements of the macular pigment are essential in both clinical and research settings. Dual wavelength fundus auto-fluorescence seems to be the optimal method. This study aims to investigate changes in fundus autofluorescence in patients taking daily lutein oral supplements and develop image processing methods for follow-up evaluations of the images. METHODS New devices allow us to examine fundus autofluorescence using both blue and green excitation wavelengths. This allows detection of the amount of macular pigment by subtracting these two images because the yellow pigment particles absorb blue wavelengths. We determined daily dose of 25 mg of lutein and 3 mg of zeaxanthin. Patients were followed up for 15 months at 3-month intervals. RESULTS During our 15-month study, we observed a positive trend in pixel lightness values, suggesting an increase in macular pigments in the foveal area. In all patients taking daily lutein supplements, the foveal index significantly increased after six months, with a median change of 0.081. We did not observe a significant change after the first three months (0.006) and only a small change between the 6th and 12th-month visits (0.012). CONCLUSION With appropriate patients and procedures for capturing autofluorescence images, this is a valuable technique for macular pigment evaluation in follow-up examinations using software image post-processing and analysis with commonly available hardware. To put this into everyday practice, developing tools to automate the assessment is necessary.
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Affiliation(s)
- Patrik Rajs
- Department of Ophthalmology, UJEP Masaryk Hospital, Krajska zdravotni, a.s., Usti nad Labem, Czech Republic
- Department of Ophthalmology, University Hospital Kralovske Vinohrady and Third Faculty of Medicine, Charles University in Prague, Czech Republic
| | - Ivana Liehneova
- Department of Ophthalmology, UJEP Masaryk Hospital, Krajska zdravotni, a.s., Usti nad Labem, Czech Republic
| | - Zbynek Stranak
- Department of Ophthalmology, University Hospital Kralovske Vinohrady and Third Faculty of Medicine, Charles University in Prague, Czech Republic
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Addo EK, Allman SJ, Arunkumar R, Gorka JE, Harrison DY, Varner MW, Bernstein PS. Systemic Effects of Prenatal Carotenoid Supplementation in the Mother and her Child: The Lutein and Zeaxanthin in Pregnancy (L-ZIP) Randomized Trial -Report Number 1. J Nutr 2023; 153:2205-2215. [PMID: 37247819 PMCID: PMC10447612 DOI: 10.1016/j.tjnut.2023.05.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 05/17/2023] [Accepted: 05/26/2023] [Indexed: 05/31/2023] Open
Abstract
BACKGROUND Adding carotenoids, particularly lutein (L) and zeaxanthin (Z), to prenatal micronutrient formulations has been promoted to enhance infant visual and neural development and to maintain maternal health. Although these claims are biologically plausible, they are not yet supported by a compelling prospective trial. OBJECTIVE We investigated the effect of prenatal carotenoid supplementation on biomarkers of maternal and infant systemic carotenoid status. METHODS We randomly assigned 47 first trimester pregnant subjects by 1:1 allocation to receive standard-of-care prenatal vitamins plus a 10 mg L and 2 mg Z softgel (the Carotenoid group) or standard-of-care prenatal vitamins with a placebo softgel (the Control group) for 6-8 mo. Maternal carotenoid concentrations in the serum and skin at the end of each trimester and postpartum were measured with HPLC and resonance Raman spectroscopy, respectively. Infants' systemic carotenoid status was assessed using similar techniques but optimized for infants. Repeated measures and paired t-tests were determined, and a P value < 0.05 was considered statistically significant. RESULTS After supplementation, there was a statistically significant increase in maternal serum L + Z concentrations, serum total carotenoid concentrations, and skin carotenoid status (P < 0.001 for all) in the Carotenoid group relative to the Control group at all study time points. Similarly, infants whose mothers were in the Carotenoid group had a significant 5-fold increase in cord blood L + Z concentrations, over a 3-fold increase in cord blood total carotenoids, and a 38% increase in skin carotenoids compared with the Control group (P < 0.0001 for all). In addition, there was a strong positive, statistically significant correlation between postpartum maternal and infant systemic carotenoid status (P < 0.0001). CONCLUSION Prenatal carotenoid supplementation significantly increased maternal and infant systemic (skin and serum) carotenoid status, which may benefit pregnant women and their infants' health. This trial was registered at clinicaltrials.gov as NCT03750968.
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Affiliation(s)
- Emmanuel K Addo
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA
| | - Susan J Allman
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Ranganathan Arunkumar
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Joanna E Gorka
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Deborah Y Harrison
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Michael W Varner
- Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA
| | - Paul S Bernstein
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA; Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA.
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Addo EK, Hartnett ME, Bernstein PS. The value of pre-symptomatic genetic risk assessment for age-related macular degeneration: the Moran AMD Genetic Testing Assessment (MAGENTA) study-a study protocol for a randomized controlled trial. Trials 2023; 24:414. [PMID: 37337222 PMCID: PMC10278319 DOI: 10.1186/s13063-023-07436-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Accepted: 06/06/2023] [Indexed: 06/21/2023] Open
Abstract
BACKGROUND Age-related macular degeneration (AMD) is an irreversible blinding eye condition with complex genetic and environmental etiologies. Genetic testing for AMD for previously identified multiple-risk single nucleotide polymorphisms can help determine an individual's future susceptibility. However, such testing has been discouraged until evidence shows that providing such information to symptomatic or pre-symptomatic individuals will alter their disease course. Therefore, we designed this study to investigate whether knowledge of AMD risk could stimulate the adoption of a healthier lifestyle that could lower the incidence of AMD later in life. We hypothesize that pre-symptomatic individuals informed of a high genetic risk of AMD are more likely to make quantifiable, positive lifestyle changes relative to participants informed of lower genetic risk or randomized to deferred disclosure of genetic testing results. METHODS The Moran AMD Genetic Testing Assessment (MAGENTA) study is a phase 2, single-center, prospective, double-masked, randomized controlled trial conducted at the John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Participants are randomized by a 3:1 allocation ratio to immediate and deferred disclosure groups and followed for 12 months. Skin, ocular, and serum carotenoid status, as well as nutritional and social surveys, are assessed at study visits. Skin carotenoid assessment is by resonance Raman spectroscopy and reflectance spectroscopy, ocular carotenoids are measured with Heidelberg Spectralis autofluorescence imaging and fluorescence lifetime imaging ophthalmoscopy (FLIO), and serum carotenoids are quantified using high-performance liquid chromatography. The primary outcome evaluates changes in skin carotenoid status in response to genetic risk disclosure. The secondary outcomes examine changes in ocular and serum carotenoid status in response to genetic risk disclosure. Also, we will correlate AMD genetic risk with baseline ocular and systemic carotenoid status and FLIO. DISCUSSION MAGENTA will provide much-needed evidence on whether pre-symptomatic testing for AMD risk can lead to quantifiable long-term changes in behavior and lifestyle associated with a lower incidence of AMD later in life. Findings from the MAGENTA trial will facilitate the design of a future larger, longer-term, multicenter phase 3 trial that could feature subgroup analysis, expanded measures of lifestyle modification, and potential active nutritional interventions. TRIAL REGISTRATION ClinicalTrials.gov NCT05265624 . Registered on March 3, 2022.
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Affiliation(s)
- Emmanuel K Addo
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA
- Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA
| | - M Elizabeth Hartnett
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA
- Department of Ophthalmology and Visual Sciences, Byers Eye Institute, Stanford University, Palo Alto, CA, USA
| | - Paul S Bernstein
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA.
- Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA.
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Li X, Holt RR, Keen CL, Morse LS, Zivkovic AM, Yiu G, Hackman RM. Potential roles of dietary zeaxanthin and lutein in macular health and function. Nutr Rev 2023; 81:670-683. [PMID: 36094616 PMCID: PMC11494239 DOI: 10.1093/nutrit/nuac076] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Lutein, zeaxanthin, and meso-zeaxanthin are three xanthophyll carotenoid pigments that selectively concentrate in the center of the retina. Humans cannot synthesize lutein and zeaxanthin, so these compounds must be obtained from the diet or supplements, with meso-zeaxanthin being converted from lutein in the macula. Xanthophylls are major components of macular pigments that protect the retina through the provision of oxidant defense and filtering of blue light. The accumulation of these three xanthophylls in the central macula can be quantified with non-invasive methods, such as macular pigment optical density (MPOD). MPOD serves as a useful tool for assessing risk for, and progression of, age-related macular degeneration, the third leading cause of blindness worldwide. Dietary surveys suggest that the dietary intakes of lutein and zeaxanthin are decreasing. In addition to low dietary intake, pregnancy and lactation may compromise the lutein and zeaxanthin status of both the mother and infant. Lutein is found in modest amounts in some orange- and yellow-colored vegetables, yellow corn products, and in egg yolks, but rich sources of zeaxanthin are not commonly consumed. Goji berries contain the highest known levels of zeaxanthin of any food, and regular intake of these bright red berries may help protect against the development of age-related macular degeneration through an increase in MPOD. The purpose of this review is to summarize the protective function of macular xanthophylls in the eye, speculate on the compounds' role in maternal and infant health, suggest the establishment of recommended dietary values for lutein and zeaxanthin, and introduce goji berries as a rich food source of zeaxanthin.
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Affiliation(s)
- Xiang Li
- are with the Department of Nutrition, UC Davis, Davis, California, USA
| | - Roberta R Holt
- are with the Department of Nutrition, UC Davis, Davis, California, USA
| | - Carl L Keen
- are with the Department of Nutrition, UC Davis, Davis, California, USA
- is with the Department of Internal Medicine, UC Davis, Sacramento, California, USA
| | - Lawrence S Morse
- are with the Department of Ophthalmology and Vision Science, UC Davis Medical Center, Sacramento, California, USA
| | - Angela M Zivkovic
- re with the Department of Nutrition, UC Davis, Davis, California, USA
| | - Glenn Yiu
- are with the Department of Ophthalmology and Vision Science, UC Davis Medical Center, Sacramento, California, USA
| | - Robert M Hackman
- are with the Department of Nutrition, UC Davis, Davis, California, USA
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Arunkumar R, Li B, Addo EK, Hartnett ME, Bernstein PS. Prenatal Carotenoid Supplementation With Lutein or Zeaxanthin Ameliorates Oxygen-Induced Retinopathy (OIR) in Bco2-/- Macular Pigment Mice. Invest Ophthalmol Vis Sci 2023; 64:9. [PMID: 37036416 PMCID: PMC10108734 DOI: 10.1167/iovs.64.4.9] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 03/19/2023] [Indexed: 04/11/2023] Open
Abstract
Purpose Premature infants at risk of retinopathy of prematurity (ROP) miss placental transfer of the carotenoids lutein (L) and zeaxanthin (Z) during the third trimester. We previously demonstrated that prenatal L and Z supplementation raised carotenoid levels in infants at birth in the Lutein and Zeaxanthin in Pregnancy (L-ZIP) study (NCT03750968). Based on their antioxidant effects and bioavailability, we hypothesized that prenatal maternal supplementation with macular carotenoids would reduce the risk of ROP. To test this hypothesis, we utilized "macular pigment mice" genetically engineered to take up L and Z into the retina in a model of oxygen-induced retinopathy (OIR). Methods Pregnant Bco2-/- mice were divided into nine experimental subgroups based on the type of supplementation (L, Z, or placebo) and on the maternal supplementation start date corresponding to the three trimesters of human fetal development (E0, E11, and P1). Pups and nursing mothers were exposed to 75% O2 for 5 days (P7-P12) and returned to room air for 5 days (P12-P17). Pups were killed at P12 and P17, and their retinas were analyzed for vaso-obliteration and intravitreal neovascularization. Results Pups of pregnant mice supplemented with L or Z had significant reductions in areas of vaso-obliteration and intravitreal neovascularization compared to placebo. Prenatal carotenoid supplementation starting at E0 or E11 was significantly more protective against OIR than postnatal supplementation starting at P1. Conclusions Prenatal supplementation with L and Z was beneficial in a mouse OIR model. We recommend testing prenatal L and Z supplementation in future human clinical trials to prevent ROP.
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Affiliation(s)
- Ranganathan Arunkumar
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah, United States
| | - Binxing Li
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah, United States
| | - Emmanuel K. Addo
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah, United States
| | - Mary Elizabeth Hartnett
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah, United States
| | - Paul S. Bernstein
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah, United States
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Li B, George EW, Vachali P, Chang FY, Gorusupudi A, Arunkumar R, Giauque NA, Wan Z, Frederick JM, Bernstein PS. Mechanism for the selective uptake of macular carotenoids mediated by the HDL cholesterol receptor SR-BI. Exp Eye Res 2023; 229:109429. [PMID: 36863431 PMCID: PMC10076185 DOI: 10.1016/j.exer.2023.109429] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 12/24/2022] [Accepted: 02/19/2023] [Indexed: 03/04/2023]
Abstract
The macular carotenoids lutein and zeaxanthin are taken up from the bloodstream into the human retina through a selective process, for which the HDL cholesterol receptor scavenger receptor BI (SR-BI) in the cells of retinal pigment epithelium (RPE) is thought to be a key mediator. However, the mechanism of SR-BI-mediated selective uptake of macular carotenoids is still not fully understood. Here, we investigate possible mechanisms using biological assays and cultured HEK293 cells, a cell line without endogenous SR-BI expression. Binding affinities between SR-BI and various carotenoids were measured by surface plasmon resonance (SPR) spectroscopy, which shows that SR-BI cannot bind lutein or zeaxanthin specifically. Overexpression of SR-BI in HEK293 cells results in more lutein and zeaxanthin taken up than β-carotene, and this effect can be eliminated by an SR-BI mutant (C384Y) whose cholesterol uptake tunnel is blocked. Next, we determined the effects of HDL and hepatic lipase (LIPC), SR-BI's partners in HDL cholesterol transport, on SR-BI-mediated carotenoid uptake. HDL addition dramatically reduced lutein, zeaxanthin, and β-carotene in HEK293 cells expressing SR-BI, but the cellular lutein and zeaxanthin are higher than β-carotene. LIPC addition increases the uptake of all three carotenoids in HDL-treated cells, and promotes the transport of lutein and zeaxanthin better than β-carotene. Our results suggest that SR-BI and its HDL cholesterol partner HDL and LIPC may be involved in the selective uptake of macular carotenoids.
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Affiliation(s)
- Binxing Li
- Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA.
| | - Evan W George
- Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA
| | - Preejith Vachali
- Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA
| | - Fu-Yen Chang
- Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA
| | - Aruna Gorusupudi
- Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA
| | - Ranganathan Arunkumar
- Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA
| | - Nathan A Giauque
- Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA
| | - Zihe Wan
- Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA
| | - Jeanne M Frederick
- Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA
| | - Paul S Bernstein
- Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA.
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11
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Yoshida T, Takagi Y, Igarashi-Yokoi T, Ohno-Matsui K. Efficacy of lutein supplements on macular pigment optical density in highly myopic individuals: A randomized controlled trial. Medicine (Baltimore) 2023; 102:e33280. [PMID: 36961139 PMCID: PMC10036027 DOI: 10.1097/md.0000000000033280] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 02/23/2023] [Indexed: 03/25/2023] Open
Abstract
INTRODUCTION Lutein supplementation is beneficial in preventing maculae from developing serious ocular diseases. This study aimed to evaluate the efficacy and safety of lutein administration in patients with high myopia (HM). METHODS In a single-center randomized double-blinded placebo-controlled trial conducted over 24 months, 22 eyes were enrolled in lutein and control groups. Among them, 15 eyes in the lutein group and 13 eyes in the control group completed the study. All patients with HM (axial length > 26.00) were administered lutein (20 mg) or placebo once daily for 6 months. The macular pigment optical density (MPOD), rate of change in MPOD, visual acuity, contrast sensitivity, and electroretinogram after administration were examined at baseline, 3 months, and 6 months. RESULTS The baseline MPOD in the control and lutein groups was 0.71 ± 0.21 and 0.70 ± 0.22, respectively. The MPOD in the control and lutein groups at 3 months was 0.70 ± 0.21 and 0.70 ± 0.25, respectively, and at 6 months was 0.66 ± 0.20 and 0.72 ± 0.27, respectively, which was not significantly different from those at baseline or between the groups. The MPOD significantly increased from baseline in the lutein group with less than 28.25 mm of axial length at 6 months (from 0.71 ± 0.20 to 0.78 ± 0.22, P = .02, t test). visual acuity, contrast sensitivity, and electroretinogram values were similar between the groups. CONCLUSION Lutein supplementation showed significant benefits in MPOD augmentation in patients with HM.
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Affiliation(s)
- Takeshi Yoshida
- Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Advanced Ophthalmic Imaging, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasutaka Takagi
- Japan Medical Affairs, Japan business, Santen Pharmaceutical Co. Ltd., Osaka, Japan
| | - Tae Igarashi-Yokoi
- Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kyoko Ohno-Matsui
- Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, Tokyo, Japan
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12
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Polyunsaturated Lipids in the Light-Exposed and Prooxidant Retinal Environment. Antioxidants (Basel) 2023; 12:antiox12030617. [PMID: 36978865 PMCID: PMC10044808 DOI: 10.3390/antiox12030617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/26/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023] Open
Abstract
The retina is an oxidative stress-prone tissue due to high content of polyunsaturated lipids, exposure to visible light stimuli in the 400–480 nm range, and high oxygen availability provided by choroidal capillaries to support oxidative metabolism. Indeed, lipids’ peroxidation and their conversion into reactive species promoting inflammation have been reported and connected to retinal degenerations. Here, we review recent evidence showing how retinal polyunsaturated lipids, in addition to oxidative stress and damage, may counteract the inflammatory response triggered by blue light-activated carotenoid derivatives, enabling long-term retina operation despite its prooxidant environment. These two aspects of retinal polyunsaturated lipids require tight control over their synthesis to avoid overcoming their protective actions by an increase in lipid peroxidation due to oxidative stress. We review emerging evidence on different transcriptional control mechanisms operating in retinal cells to modulate polyunsaturated lipid synthesis over the life span, from the immature to the ageing retina. Finally, we discuss the antioxidant role of food nutrients such as xanthophylls and carotenoids that have been shown to empower retinal cells’ antioxidant responses and counteract the adverse impact of prooxidant stimuli on sight.
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13
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Protein-Mediated Carotenoid Delivery Suppresses the Photoinducible Oxidation of Lipofuscin in Retinal Pigment Epithelial Cells. Antioxidants (Basel) 2023; 12:antiox12020413. [PMID: 36829973 PMCID: PMC9952040 DOI: 10.3390/antiox12020413] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 01/31/2023] [Accepted: 02/03/2023] [Indexed: 02/10/2023] Open
Abstract
Lipofuscin of retinal pigment epithelium (RPE) cells is a complex heterogeneous system of chromophores which accumulates as granules during the cell's lifespan. Lipofuscin serves as a source of various cytotoxic effects linked with oxidative stress. Several age-related eye diseases such as macular degeneration of the retina, as well as some severe inherited eye pathologies, are accompanied by a significant increase in lipofuscin granule concentration. The accumulation of carotenoids in the RPE could provide an effective antioxidant protection against lipofuscin cytotoxic manifestations. Given the highly lipophilic nature of carotenoids, their targeted delivery to the vulnerable tissues can potentially be assisted by special proteins. In this study, we demonstrate how protein-mediated delivery of zeaxanthin using water-soluble Bombyx mori carotenoid-binding protein (BmCBP-ZEA) suppresses the photoinducible oxidative stress in RPE cells caused by irradiation of lipofuscin with intense white light. We implemented fluorescence lifetime imaging of the RPE cell culture ARPE-19 fed with lipofuscin granules and then irradiated by white light with and without the addition of BmCBP-ZEA. We demonstrate that after irradiation the mean fluorescence lifetime of lipofuscin significantly increases, while the presence of BmCBP-ZEA at 200 nM concentration suppresses the increase in the average lifetime of lipofuscin fluorescence, indicating an approx. 35% inhibition of the oxidative stress. This phenomenon serves as indirect yet important evidence of the efficiency of the protein-mediated carotenoid delivery into pigment epithelium cells.
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14
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Arunkumar R, Bernstein PS. Macular Pigment Carotenoids and Bisretinoid A2E. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1415:15-20. [PMID: 37440008 DOI: 10.1007/978-3-031-27681-1_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Abstract
Lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ) are the three macular pigments (MP) carotenoids that uniquely accumulate in the macula lutea region of the human retina. L and Z are obtained by humans through dietary intake. The third MP, MZ, is rarely present in diet, and its abundance in the human fovea is due to the metabolic conversion of dietary L by the retinal pigment epithelium's RPE65 enzyme. The major functions of MP in ocular health are to filter high-intensity, phototoxic blue light and to act as effective antioxidants for scavenging free radicals. The pyridinium bisretinoid, N-retinylidene-N-retinylethanolamine (A2E), contributes to drusen formation in dry age-related macular degeneration (AMD) and to the autofluorescent flecks in autosomal recessive Stargardt disease (STGD1). Retinal carotenoids attenuate A2E formation and can directly and indirectly alleviate A2E-mediated oxidative damage. In this chapter, we review these more recently recognized interconnections between MP carotenoids and A2E bisretinoids.
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Affiliation(s)
- Ranganathan Arunkumar
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA
| | - Paul S Bernstein
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA.
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15
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Udensi J, Loughman J, Loskutova E, Byrne HJ. Raman Spectroscopy of Carotenoid Compounds for Clinical Applications-A Review. Molecules 2022; 27:9017. [PMID: 36558154 PMCID: PMC9784873 DOI: 10.3390/molecules27249017] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/09/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022] Open
Abstract
Carotenoid compounds are ubiquitous in nature, providing the characteristic colouring of many algae, bacteria, fruits and vegetables. They are a critical component of the human diet and play a key role in human nutrition, health and disease. Therefore, the clinical importance of qualitative and quantitative carotene content analysis is increasingly recognised. In this review, the structural and optical properties of carotenoid compounds are reviewed, differentiating between those of carotenes and xanthophylls. The strong non-resonant and resonant Raman spectroscopic signatures of carotenoids are described, and advances in the use of Raman spectroscopy to identify carotenoids in biological environments are reviewed. Focus is drawn to applications in nutritional analysis, optometry and serology, based on in vitro and ex vivo measurements in skin, retina and blood, and progress towards establishing the technique in a clinical environment, as well as challenges and future perspectives, are explored.
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Affiliation(s)
- Joy Udensi
- FOCAS Research Institute, Technological University Dublin, City Campus, Camden Row, Dublin 8, D08 CKP1 Dublin, Ireland
- School of Physics and Clinical and Optometric Sciences, Technological University Dublin, City Campus, Grangegorman, Dublin 7, D07 EWV4 Dublin, Ireland
- Centre for Eye Research, Ireland, Technological University Dublin, City Campus, Grangegorman, Dublin 7, D07 EWV4 Dublin, Ireland
| | - James Loughman
- School of Physics and Clinical and Optometric Sciences, Technological University Dublin, City Campus, Grangegorman, Dublin 7, D07 EWV4 Dublin, Ireland
- Centre for Eye Research, Ireland, Technological University Dublin, City Campus, Grangegorman, Dublin 7, D07 EWV4 Dublin, Ireland
| | - Ekaterina Loskutova
- School of Physics and Clinical and Optometric Sciences, Technological University Dublin, City Campus, Grangegorman, Dublin 7, D07 EWV4 Dublin, Ireland
- Centre for Eye Research, Ireland, Technological University Dublin, City Campus, Grangegorman, Dublin 7, D07 EWV4 Dublin, Ireland
| | - Hugh J. Byrne
- FOCAS Research Institute, Technological University Dublin, City Campus, Camden Row, Dublin 8, D08 CKP1 Dublin, Ireland
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16
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Obana A, Asaoka R, Miura A, Nozue M, Takayanagi Y, Nakamura M. Improving Skin Carotenoid Levels in Young Students through Brief Dietary Education Using the Veggie Meter. Antioxidants (Basel) 2022; 11:antiox11081570. [PMID: 36009289 PMCID: PMC9405129 DOI: 10.3390/antiox11081570] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 08/09/2022] [Accepted: 08/12/2022] [Indexed: 11/25/2022] Open
Abstract
The antioxidant and anti-inflammatory effects of carotenoid have been determined to aid in the prevention of a wide range of oxidative disorders, arteriosclerosis, obesity, and various types of cancers. In order to keep high carotenoid levels in the body, much of the vegetable and fruit (V/F) intake is mandatory. However, the actual intake of V/F is not enough in many countries. The aim of this study was to assess whether brief dietary education using the Veggie Meter (VM) that could measure skin carotenoid (SC) levels could induce the increase in carotenoid levels via V/F intake. Two hundred and sixty-one elementary and junior high school students (ages 7−14 years old) received brief educational session and SC evaluation by VM, and the changes in SC levels were examined after 6 months. The baseline VM scores ranged from 131 to 825, and the average significantly increased from 400.0 ± 124.7 (standard deviation) to 447.4 ± 140.4 at Month 6 (p < 0.0001). The percentage of increase at month 6 was negatively correlated with the baseline values (r = −0.36, p < 0.0001). This finding implies that subjects who became aware of their inferiority tended to make a significant effort to change their behavior. The multivariate logistic regression analysis demonstrated that subjects taking much of green and yellow vegetables, drinking vegetable/tomato juice, and eating any fruit had higher VM scores than the average value. In conclusion, the educational approach using VM was supposed to be an effective method of raising awareness of the V/F shortage and increasing V/F intake that could indue the increase in SC levels.
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Affiliation(s)
- Akira Obana
- Department of Ophthalmology, Seirei Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Naka-ku, Hamamatsu City 430-8558, Shizuoka, Japan
- Department of Medical Spectroscopy, Institute for Medical Photonics Research, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu City 431-3192, Shizuoka, Japan
- Correspondence: ; Tel.: +81-53-474-2222
| | - Ryo Asaoka
- Department of Ophthalmology, Seirei Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Naka-ku, Hamamatsu City 430-8558, Shizuoka, Japan
| | - Ayako Miura
- Faculty of Health Promotion Sciences, Department of Health and Nutritional Sciences, Tokoha University, 1230 Miyakoda-cho, Kita-ku, Hamamatsu City 431-2102, Shizuoka, Japan
| | - Miho Nozue
- Faculty of Health Promotion Sciences, Department of Health and Nutritional Sciences, Tokoha University, 1230 Miyakoda-cho, Kita-ku, Hamamatsu City 431-2102, Shizuoka, Japan
| | - Yuji Takayanagi
- Department of Ophthalmology, Seirei Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Naka-ku, Hamamatsu City 430-8558, Shizuoka, Japan
| | - Mieko Nakamura
- Department of Community Health & Preventive Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu City 431-3192, Shizuoka, Japan
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17
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Arunkumar R, Gorusupudi A, Li B, Blount JD, Nwagbo U, Kim HJ, Sparrow JR, Bernstein PS. Lutein and zeaxanthin reduce A2E and iso-A2E levels and improve visual performance in Abca4 -/-/Bco2 -/- double knockout mice. Exp Eye Res 2021; 209:108680. [PMID: 34161819 PMCID: PMC8595537 DOI: 10.1016/j.exer.2021.108680] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 06/08/2021] [Accepted: 06/17/2021] [Indexed: 10/21/2022]
Abstract
Accumulation of bisretinoids such as A2E and its isomer iso-A2E is thought to mediate blue light-induced oxidative damage associated with age-related macular degeneration (AMD) and autosomal recessive Stargardt disease (STGD1). We hypothesize that increasing dietary intake of the macular carotenoids lutein and zeaxanthin in individuals at risk of AMD and STGD1 can inhibit the formation of bisretinoids A2E and iso-A2E, which can potentially ameliorate macular degenerative diseases. To study the beneficial effect of macular carotenoids in a retinal degenerative diseases model, we used ATP-binding cassette, sub-family A member 4 (Abca4-/-)/β,β-carotene-9',10'-oxygenase 2 (Bco2-/-) double knockout (KO) mice that accumulate elevated levels of A2E and iso-A2E in the retinal pigment epithelium (RPE) and macular carotenoids in the retina. Abca4-/-/Bco2-/- and Abca4-/- mice were fed a lutein-supplemented chow, zeaxanthin-supplemented chow or placebo chow (~2.6 mg of carotenoid/mouse/day) for three months. Visual function and electroretinography (ERG) were measured after one month and three months of carotenoid supplementation. The lutein and zeaxanthin supplemented Abca4-/-/Bco2-/- mice had significantly lower levels of RPE/choroid A2E and iso-A2E compared to control mice fed with placebo chow and improved visual performance. Carotenoid supplementation in Abca4-/- mice minimally raised retinal carotenoid levels and did not show much difference in bisretinoid levels or visual function compared to the control diet group. There was a statistically significant inverse correlation between carotenoid levels in the retina and A2E and iso-A2E levels in the RPE/choroid. Supplementation with retinal carotenoids, especially zeaxanthin, effectively inhibits bisretinoid formation in a mouse model of STGD1 genetically enhanced to accumulate carotenoids in the retina. These results provide further impetus to pursue oral carotenoids as therapeutic interventions for STGD1 and AMD.
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Affiliation(s)
- Ranganathan Arunkumar
- Department of Ophthalmology and Visual Science, John A. Moran Eye Center, University of Utah, School of Medicine, Salt Lake City, UT, USA
| | - Aruna Gorusupudi
- Department of Ophthalmology and Visual Science, John A. Moran Eye Center, University of Utah, School of Medicine, Salt Lake City, UT, USA
| | - Binxing Li
- Department of Ophthalmology and Visual Science, John A. Moran Eye Center, University of Utah, School of Medicine, Salt Lake City, UT, USA
| | - J David Blount
- Department of Ophthalmology and Visual Science, John A. Moran Eye Center, University of Utah, School of Medicine, Salt Lake City, UT, USA
| | - Uzoamaka Nwagbo
- Department of Ophthalmology and Visual Science, John A. Moran Eye Center, University of Utah, School of Medicine, Salt Lake City, UT, USA
| | - Hye Jin Kim
- Department of Ophthalmology, Columbia University Medical Center, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA
| | - Janet R Sparrow
- Department of Ophthalmology, Columbia University Medical Center, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA
| | - Paul S Bernstein
- Department of Ophthalmology and Visual Science, John A. Moran Eye Center, University of Utah, School of Medicine, Salt Lake City, UT, USA.
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18
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Green-Gomez M, Moran R, Stringham J, Hernández-Alcaraz C, Mendoza-Herrera K, Fromow-Guerra JJ, Prado-Cabrero A, Nolan J. Environmental and Nutritional Determinants of Macular Pigment in a Mexican Population. Invest Ophthalmol Vis Sci 2021; 62:18. [PMID: 34241622 PMCID: PMC8288050 DOI: 10.1167/iovs.62.9.18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 05/21/2021] [Indexed: 01/23/2023] Open
Abstract
Purpose The carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin deposit at the macula as macular pigment (MP) and provide visual benefits and protection against macular diseases. The present study investigated MP, its nutritional and environmental determinants, and its constituent carotenoids in serum from a Mexican sample, in healthy participants and with metabolic diseases. Additionally, we compared these variables with an Irish sample. Methods MP was measured in 215 subjects from a rural community in Mexico with dual-wavelength autofluorescence imaging reported as MP optical volume (MPOV). Dietary intake and serum concentrations of L and Z were evaluated. Results The mean MPOV was 8429 (95% confidence interval, 8060-8797); range. 1171-15,976. The mean L and Z serum concentrations were 0.25 ± 0.15 µmol/L and 0.09 ± 0.04 µmol/L, respectively. The MPOV was positively correlated with L and Z serum concentrations (r = 0.347; P < 0.001 and r = 0.311; P < 0.001, respectively), but not with L + Z dietary estimates. Subjects with daily sunlight exposure of more than 50% were found to have significantly higher MPOV than those with less than 50% (P = 0.005). MPOV and serum concentrations of L and Z were significantly higher in the Mexican sample compared with the Irish sample, but this difference was not reflected in dietary analysis. Conclusions These new data from a Mexican sample provide evidence of the multifactorial interactions and environmental determinants of MP such as sunlight exposure and dietary patterns. These findings will be essential for future studies in Mexico for eye health, visual function, and ocular pathology.
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Affiliation(s)
- Marina Green-Gomez
- Nutrition Research Centre Ireland, School of Health Science, Waterford Institute of Technology, Waterford, Ireland
| | - Rachel Moran
- Nutrition Research Centre Ireland, School of Health Science, Waterford Institute of Technology, Waterford, Ireland
| | - James Stringham
- Nutrition Research Centre Ireland, School of Health Science, Waterford Institute of Technology, Waterford, Ireland
| | - Cesar Hernández-Alcaraz
- Centro de Investigación en Nutrición y Salud, Instituto Nacional de Salud Pública, Cuernavaca, México
| | - Kenny Mendoza-Herrera
- Centro de Investigación en Nutrición y Salud, Instituto Nacional de Salud Pública, Cuernavaca, México
| | - J Jans Fromow-Guerra
- Retina Division, Asociación Para Evitar la Ceguera en México I.A.P., México City, México
| | - Alfonso Prado-Cabrero
- Nutrition Research Centre Ireland, School of Health Science, Waterford Institute of Technology, Waterford, Ireland
| | - John Nolan
- Nutrition Research Centre Ireland, School of Health Science, Waterford Institute of Technology, Waterford, Ireland
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19
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Luchowski R, Grudzinski W, Welc R, Mendes Pinto MM, Sek A, Ostrowski J, Nierzwicki L, Chodnicki P, Wieczor M, Sowinski K, Rejdak R, Juenemann AGM, Teresinski G, Czub J, Gruszecki WI. Light-Modulated Sunscreen Mechanism in the Retina of the Human Eye. J Phys Chem B 2021; 125:6090-6102. [PMID: 34038114 PMCID: PMC8279541 DOI: 10.1021/acs.jpcb.1c01198] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
The functioning of the human eye in the extreme range of light intensity requires a combination of the high sensitivity of photoreceptors with their photostability. Here, we identify a regulatory mechanism based on dynamic modulation of light absorption by xanthophylls in the retina, realized by reorientation of pigment molecules induced by trans-cis photoisomerization. We explore this photochemically switchable system using chromatographic analysis coupled with microimaging based on fluorescence lifetime and Raman scattering, showing it at work in both isolated human retina and model lipid membranes. The molecular mechanism underlying xanthophyll reorientation is explained in terms of hydrophobic mismatch using molecular dynamics simulations. Overall, we show that xanthophylls in the human retina act as "molecular blinds", opening and closing on a submillisecond timescale to dynamically control the intensity of light reaching the photoreceptors, thus enabling vision at a very low light intensity and protecting the retina from photodegradation when suddenly exposed to strong light.
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Affiliation(s)
- Rafal Luchowski
- Department of Biophysics, Institute of Physics, Maria Curie-Sklodowska University, Pl. M. Curie-Sklodowskiej 1, 20-031 Lublin, Poland
| | - Wojciech Grudzinski
- Department of Biophysics, Institute of Physics, Maria Curie-Sklodowska University, Pl. M. Curie-Sklodowskiej 1, 20-031 Lublin, Poland
| | - Renata Welc
- Department of Biophysics, Institute of Physics, Maria Curie-Sklodowska University, Pl. M. Curie-Sklodowskiej 1, 20-031 Lublin, Poland
| | - Maria Manuela Mendes Pinto
- Department of Biophysics, Institute of Physics, Maria Curie-Sklodowska University, Pl. M. Curie-Sklodowskiej 1, 20-031 Lublin, Poland
| | - Alicja Sek
- Department of Biophysics, Institute of Physics, Maria Curie-Sklodowska University, Pl. M. Curie-Sklodowskiej 1, 20-031 Lublin, Poland.,Department of Interfacial Phenomena, Institute of Chemical Sciences, Faculty of Chemistry, Maria Curie-Sklodowska University, Pl. M. Curie-Sklodowskiej 3, 20-031 Lublin, Poland
| | - Jan Ostrowski
- Department of General Ophthalmology, Medical University of Lublin, Chmielna 1, 20-079 Lublin, Poland
| | - Lukasz Nierzwicki
- Department of Physical Chemistry, Gdansk University of Technology, Narutowicza 11/12, 80-233 Gdansk, Poland
| | - Pawel Chodnicki
- Department of Physical Chemistry, Gdansk University of Technology, Narutowicza 11/12, 80-233 Gdansk, Poland
| | - Milosz Wieczor
- Department of Physical Chemistry, Gdansk University of Technology, Narutowicza 11/12, 80-233 Gdansk, Poland
| | - Karol Sowinski
- Department of Biophysics, Institute of Physics, Maria Curie-Sklodowska University, Pl. M. Curie-Sklodowskiej 1, 20-031 Lublin, Poland
| | - Robert Rejdak
- Department of General Ophthalmology, Medical University of Lublin, Chmielna 1, 20-079 Lublin, Poland
| | | | - Grzegorz Teresinski
- Department of Forensic Medicine, Medical University of Lublin, Jaczewskiego 8b, 20-090 Lublin, Poland
| | - Jacek Czub
- Department of Physical Chemistry, Gdansk University of Technology, Narutowicza 11/12, 80-233 Gdansk, Poland
| | - Wieslaw I Gruszecki
- Department of Biophysics, Institute of Physics, Maria Curie-Sklodowska University, Pl. M. Curie-Sklodowskiej 1, 20-031 Lublin, Poland
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Addo EK, Gorusupudi A, Allman S, Bernstein PS. The Lutein and Zeaxanthin in Pregnancy (L-ZIP) study-carotenoid supplementation during pregnancy: ocular and systemic effects-study protocol for a randomized controlled trial. Trials 2021; 22:300. [PMID: 33888136 PMCID: PMC8063287 DOI: 10.1186/s13063-021-05244-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 03/31/2021] [Indexed: 12/02/2022] Open
Abstract
Background Lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), collectively called the macular pigment (MP), are dietary carotenoids that preferentially localize in the macula of the human eye. MP protects the macula from photo-oxidative damage and enhances visual function. Inadequate maternal intake of carotenoids, coupled with the placental transfer of maternal carotenoids to support fetal brain and retina development, potentially put mothers at risk of depletion systemically and in their ocular tissues. Presently, maternal carotenoid status throughout pregnancy remains poorly characterized, and no prospective randomized controlled trial of L and Z supplementation via prenatal vitamins has assessed maternal and infants’ systemic and ocular carotenoid status during pregnancy. We hypothesize that prenatal maternal carotenoid supplementation will counteract maternal carotenoid depletion during pregnancy and will improve biomarkers of carotenoid status of both mothers and infants. Methods Lutein and Zeaxanthin in Pregnancy (L-ZIP) is a phase 2, single-center, prospective, double-masked, randomized active-controlled clinical trial conducted at the John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA. Participants consume a daily standard prenatal multivitamin with no added carotenoids and are randomized (1:1 allocation) to receive either a capsule containing 10 mg L and 2 mg Z in safflower oil (Carotenoid group) or a capsule containing only safflower oil with no added carotenoids (Control group) for a period of 6 to 8 months. Skin, serum, and ocular carotenoids are measured at every study visit (i.e., within the first trimester [baseline], second trimester, third trimester, and 0–2 weeks postpartum). Skin carotenoid assessment is by resonance Raman spectroscopy (RRS); serum carotenoid status is quantified using high-performance liquid chromatography (HPLC); and MP is measured with the dual-wavelength autofluorescence. Infants’ MP and foveal anatomy are assessed using RetCam retinal camera and Bioptigen SD-OCT, respectively. The primary outcomes are changes in maternal systemic and ocular carotenoid status during pregnancy. Discussion L-ZIP is the first prospective RCT to investigate maternal carotenoid status throughout pregnancy and to determine whether prenatal maternal carotenoid supplementation will offset maternal carotenoid depletion and improve biomarkers of maternal and infant’s carotenoid status. Findings from L-ZIP will strengthen recommendations regarding prenatal carotenoid supplementation and consequently inform policy decisions. Trial registration ClinicalTrials.gov NCT03750968. Registered on November 23, 2018
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Affiliation(s)
- Emmanuel Kofi Addo
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA.,Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA
| | - Aruna Gorusupudi
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA
| | - Susan Allman
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA
| | - Paul S Bernstein
- Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, 65 Mario Capecchi Drive, Salt Lake City, UT, 84132, USA. .,Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA.
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21
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Widomska J, Gruszecki WI, Subczynski WK. Factors Differentiating the Antioxidant Activity of Macular Xanthophylls in the Human Eye Retina. Antioxidants (Basel) 2021; 10:601. [PMID: 33919673 PMCID: PMC8070478 DOI: 10.3390/antiox10040601] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 04/01/2021] [Accepted: 04/07/2021] [Indexed: 02/06/2023] Open
Abstract
Macular xanthophylls, which are absorbed from the human diet, accumulate in high concentrations in the human retina, where they efficiently protect against oxidative stress that may lead to retinal damage. In addition, macular xanthophylls are uniquely spatially distributed in the retina. The zeaxanthin concentration (including the lutein metabolite meso-zeaxanthin) is ~9-fold greater than lutein concentration in the central fovea. These numbers do not correlate at all with the dietary intake of xanthophylls, for which there is a dietary zeaxanthin-to-lutein molar ratio of 1:12 to 1:5. The unique spatial distributions of macular xanthophylls-lutein, zeaxanthin, and meso-zeaxanthin-in the retina, which developed during evolution, maximize the protection of the retina provided by these xanthophylls. We will correlate the differences in the spatial distributions of macular xanthophylls with their different antioxidant activities in the retina. Can the major protective function of macular xanthophylls in the retina, namely antioxidant actions, explain their evolutionarily determined, unique spatial distributions? In this review, we will address this question.
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Affiliation(s)
- Justyna Widomska
- Department of Biophysics, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland
| | - Wieslaw I. Gruszecki
- Department of Biophysics, Institute of Physics, Maria Curie-Sklodowska University, 20-031 Lublin, Poland;
| | - Witold K. Subczynski
- Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA;
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22
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Bernstein PS, Arunkumar R. The emerging roles of the macular pigment carotenoids throughout the lifespan and in prenatal supplementation. J Lipid Res 2021; 62:100038. [PMID: 32709621 PMCID: PMC7933486 DOI: 10.1194/jlr.tr120000956] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 07/17/2020] [Indexed: 02/06/2023] Open
Abstract
Since the publication of the Age-Related Eye Disease Study 2 (AREDS2) in 2013, the macular pigment carotenoids lutein (L) and zeaxanthin (Z) have become well known to both the eye care community and the public. It is a fascinating aspect of evolution that primates have repurposed photoprotective pigments and binding proteins from plants and insects to protect and enhance visual acuity. Moreover, utilization of these plant-derived nutrients has been widely embraced for preventing vision loss from age-related macular degeneration. More recently, there has been growing awareness that these nutrients can also play a role in improving visual performance in adults. On the other hand, the potential benefits of L and Z supplementation at very young ages have been underappreciated. In this review, we examine the biochemical mechanisms and supportive data for L and Z supplementation throughout the lifespan, with particular emphasis on prenatal supplementation. We propose that prenatal nutritional recommendations may aim at improving maternal and infant carotenoid status. Prenatal supplementation with L and Z might enhance infant visual development and performance and may even prevent retinopathy of prematurity, possibilities that should be examined in future clinical studies.
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Affiliation(s)
- Paul S Bernstein
- Department of Ophthalmology and Visual Science, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA.
| | - Ranganathan Arunkumar
- Department of Ophthalmology and Visual Science, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA
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23
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Alshammari RH, Rajesh UC, Morgan DG, Zaleski JM. Au-Cu@PANI Alloy Core Shells for Aerobic Fibrin Degradation under Visible Light Exposure. ACS APPLIED BIO MATERIALS 2020; 3:7631-7638. [PMID: 35019503 DOI: 10.1021/acsabm.0c00833] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Fibrin plays a critical role in wound healing and hemostasis, yet it is also the main case of cardiovascular diseases and thrombosis. Here, we show the unique design of Au-Cu@PANI alloy core-shell rods for fibrin clot degradation. Microscopic (transmission electron microscopy (TEM), scanning transmission electron microscopy-energy-dispersive X-ray (STEM-EDX)) and structural characterizations (powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS)) of the Au-Cu@PANI hybrid material reveal the formation of Au-Cu heterogeneous alloy core rods (aspect ratio = 3.7) with thin Cu2O and PANI shells that create a positive surface charge (ζ-potential = +22 mV). This architecture is supported by the survey XPS spectrum showing the presence of Cu 2p, N 1s, and C 1s features with binding energies of 934.8, 399.7, and 284.8 eV, respectively. Upon photolysis (λ ≥ 495 or 590 nm), these hybrid composite nanorods provide sufficient excited-state redox potential to generate reactive oxygen species (ROS) for degradation of model fibrin clots within 5-7 h. Detailed scanning electron microscopy (SEM) analysis of the fibrin network shows significant morphology modification including formation of large voids and strand termini, indicating degradation of fibrin protofibril by Au-Cu@PANI. The dye 1,3-diphenylisobenzofuran (DPBF) used to detect the presence of 1O2 shows a 27% bleaching of the absorption at λ = 418 nm within 75 min of irradiation of an aqueous Au-Cu@PANI solution in air. Moreover, electron paramagnetic resonance (EPR) spin-trapping experiments reveal a hyperfine-coupled triplet signature at room temperature with intensities 1:1:1: and g-value = 2.0057, characteristic of the reaction between the spin probe 4-Oxo-TEMP and 1O2 during irradiation. Controlled 1O2 scavenging experiments by NaN3 show 82% reduction in the spin-trapped EPR signal area. Both DPBF bleaching and EPR spin trapping indicate that in situ generated 1O2 is responsible for fibrin strand scission. This unique nanomaterial function via use of ubiquitous oxygen as a reagent could open creative avenues for future in vivo biomedical applications to treat fibrin clot diseases.
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Affiliation(s)
- Riyadh H Alshammari
- Department of Chemistry, Indiana University, Bloomington, Indiana 47405, United States.,Department of Chemistry, King Saud University, Riyadh 11451, Saudi Arabia
| | - U Chinna Rajesh
- Department of Chemistry, Indiana University, Bloomington, Indiana 47405, United States
| | - David Gene Morgan
- Electron Microscopy Center, Indiana University, Bloomington, Indiana 47405, United States
| | - Jeffrey M Zaleski
- Department of Chemistry, Indiana University, Bloomington, Indiana 47405, United States
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24
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Mansour AT, El-feky MMM, El-Beltagi HS, Sallam AE. Synergism of Dietary Co-Supplementation with Lutein and Bile Salts Improved the Growth Performance, Carotenoid Content, Antioxidant Capacity, Lipid Metabolism, and Lipase Activity of the Marbled Spinefoot Rabbitfish, Siganus rivulatus. Animals (Basel) 2020; 10:E1643. [PMID: 32932710 PMCID: PMC7552308 DOI: 10.3390/ani10091643] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 09/09/2020] [Accepted: 09/10/2020] [Indexed: 12/11/2022] Open
Abstract
A 60-day feeding trial was conducted to assess the effects of dietary supplementation with bile salts (BS), lutein (LTN), and their combination on growth, survival, carotenoid content, and antioxidant status of rabbitfish (Siganus rivulatus) larvae. Fish were fed four isonitrogenous (34.39% protein) and isoenergetic (20.57 kJ/g) diets supplemented with BS (0.15 g kg-1), LTN (0.1 g kg-1), BS+LTN (0.15 and 0.1 g kg-1, respectively), and a non-supplemented control diet. The results revealed that fish fed BS+LTN had the highest significant specific growth rate (4.37% day-1), feed efficiency (46.55%), and survival (97.78%). Lutein supplementation improved whole-body protein content, meanwhile, fish fed a BS-supplemented diet had a higher lipid content. The carotenoid deposition was significantly increased with LTN and BS+LTN in skin, muscle, and whole body compared to the control and BS treatment. All dietary supplementation of BS and LTN showed significant improvement in total antioxidant capacity, catalase, and glutathione peroxidase activities. Additionally, LTN alone or BS+LTN significantly reduced malondialdehyde levels by 5.30 and 29.91%, respectively compared to the control. BS supplementation modulated aminopeptidases activities, triglycerides, cholesterol, and increased the activity of pancreatic lipase. Therefore, it could be inferred that dietary supplementation with LTN in combination with BS could improve the growth performance, carotenoid deposition, antioxidant status, lipid digestion, and metabolism of S. rivulatus.
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Affiliation(s)
- Abdallah Tageldein Mansour
- Animal and fish Production Department, College of Agricultural and Food Sciences, King Faisal University, P.O. Box 420, Al-Ahsa 31982, Saudi Arabia
- Fish and Animal Production Department, Faculty of Agriculture (Saba Basha), Alexandria University, Alexandria 21531, Egypt
| | | | - Hossam S. El-Beltagi
- Agricultural Biotechnology Department, College of Agriculture and Food Sciences, King Faisal University, P.O. Box 420, Al-Ahsa 31982, Saudi Arabia;
- Biochemistry Department, Faculty of Agriculture, Cairo University, Gamma St.Giza 12613, Egypt
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Imaging lutein and zeaxanthin in the human retina with confocal resonance Raman microscopy. Proc Natl Acad Sci U S A 2020; 117:12352-12358. [PMID: 32409609 DOI: 10.1073/pnas.1922793117] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Lutein and zeaxanthin are xanthophyll carotenoids that are highly concentrated in the human macula, where they protect the eye from oxidative damage and improve visual performance. Distinguishing lutein from zeaxanthin in images of the human retina in vivo or in donor eye tissues has been challenging because no available technology has been able to reliably differentiate between these two carotenoids, which differ only in the position of one C = C bond. Here, we report the differential distributions of lutein and zeaxanthin in human donor retinas mapped with confocal resonance Raman microscopy. Zeaxanthin is highly concentrated in the fovea, extending from the inner to the outer limiting membranes, with especially high concentrations in the outer plexiform layer, while lutein is much more diffuse at relatively lower concentration. Our results imply that zeaxanthin may play a more important role than lutein in human macular health and disease.
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26
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Feng L, Nie K, Jiang H, Fan W. Effects of lutein supplementation in age-related macular degeneration. PLoS One 2019; 14:e0227048. [PMID: 31887124 PMCID: PMC6936877 DOI: 10.1371/journal.pone.0227048] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 12/11/2019] [Indexed: 02/05/2023] Open
Abstract
The purpose of this meta-analysis was to evaluate the effects of lutein supplementation on macular pigment optical density (MPOD) in randomized controlled trials involving patients with age-related macular degeneration (AMD). A comprehensive search of the literature was performed in PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wan Fang database through December 2018. Nine randomized controlled trials involving 920 eyes (855 with AMD) were included. Meta-analysis suggested that lutein supplementation (10 or 20 mg per day) was associated with an increase in MPOD (mean difference (MD) 0.07; 95% confidence interval (CI) 0.03 to 0.10), visual acuity (MD 0.28; 95%CI 0.06 to 0.50) and contrast sensitivity (MD 0.26; 95%CI 0.22 to 0.30). Stratified analyses showed the increase in MPOD to be faster and greater with higher dose and longer treatment. The available evidence suggests that dietary lutein may be beneficial to AMD patients and the higher dose could make MPOD increase in a shorter time.
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Affiliation(s)
- Liwen Feng
- Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
- Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Kailai Nie
- Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
- Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Hui Jiang
- Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Wei Fan
- Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
- * E-mail:
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Beluska-Turkan K, Korczak R, Hartell B, Moskal K, Maukonen J, Alexander DE, Salem N, Harkness L, Ayad W, Szaro J, Zhang K, Siriwardhana N. Nutritional Gaps and Supplementation in the First 1000 Days. Nutrients 2019; 11:E2891. [PMID: 31783636 PMCID: PMC6949907 DOI: 10.3390/nu11122891] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 11/13/2019] [Accepted: 11/19/2019] [Indexed: 12/23/2022] Open
Abstract
Optimized nutrition during the first 1000 days (from conception through the 2nd birthday) is critical for healthy development and a healthy life for the newborn. Pregnancy and the postpartum period are accompanied by physiological changes, increased energy needs, and changing requirements in the nutrients critical for optimal growth and development. Infants and toddlers also experience physiological changes and have specific nutritional needs. Food and nutrition experts can provide women of childbearing age with adequate dietary advice to optimize nutrition, as well as guidance on selecting appropriate dietary supplements. Considering the approaching 2020-2025 Dietary Guidelines for Americans (DGA) will be making specific recommendations for children, it is important to provide accurate scientific information to support health influencers in the field of nutrition. The purpose of this review is to summarize the nutrition and supplementation literature for the first 1000 days; to highlight nutritional and knowledge gaps; and to educate nutrition influencers to provide thoughtful guidance to mothers and families. Optimal nutrition during pregnancy through early childhood is critical for supporting a healthy life. Nutrition influencers, such as dietitians, obstetricians/gynecologists, and other relevant health professionals, should continue guiding supplement and food intake and work closely with expectant families and nutrition gatekeepers.
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Affiliation(s)
- Katrina Beluska-Turkan
- Church & Dwight, Co., Inc., Product Development Nutritional Sciences, Princeton, NJ 08540, USA; (K.B.-T.); (K.M.); (L.H.); (W.A.); (J.S.); (K.Z.)
| | - Renee Korczak
- Premier Nutrition, LLC, Bernardsville, NJ 07924, USA;
| | - Beth Hartell
- PearTree Nutrition, LLC, Seattle, WA 98115, USA;
| | - Kristin Moskal
- Church & Dwight, Co., Inc., Product Development Nutritional Sciences, Princeton, NJ 08540, USA; (K.B.-T.); (K.M.); (L.H.); (W.A.); (J.S.); (K.Z.)
| | | | | | - Norman Salem
- DSM Nutritional Products, Columbia, MD 21045, USA;
| | - Laura Harkness
- Church & Dwight, Co., Inc., Product Development Nutritional Sciences, Princeton, NJ 08540, USA; (K.B.-T.); (K.M.); (L.H.); (W.A.); (J.S.); (K.Z.)
| | - Wafaa Ayad
- Church & Dwight, Co., Inc., Product Development Nutritional Sciences, Princeton, NJ 08540, USA; (K.B.-T.); (K.M.); (L.H.); (W.A.); (J.S.); (K.Z.)
| | - Jacalyn Szaro
- Church & Dwight, Co., Inc., Product Development Nutritional Sciences, Princeton, NJ 08540, USA; (K.B.-T.); (K.M.); (L.H.); (W.A.); (J.S.); (K.Z.)
| | - Kelly Zhang
- Church & Dwight, Co., Inc., Product Development Nutritional Sciences, Princeton, NJ 08540, USA; (K.B.-T.); (K.M.); (L.H.); (W.A.); (J.S.); (K.Z.)
| | - Nalin Siriwardhana
- Church & Dwight, Co., Inc., Product Development Nutritional Sciences, Princeton, NJ 08540, USA; (K.B.-T.); (K.M.); (L.H.); (W.A.); (J.S.); (K.Z.)
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Green-Gomez M, Bernstein PS, Curcio CA, Moran R, Roche W, Nolan JM. Standardizing the Assessment of Macular Pigment Using a Dual-Wavelength Autofluorescence Technique. Transl Vis Sci Technol 2019; 8:41. [PMID: 31867142 PMCID: PMC6922273 DOI: 10.1167/tvst.8.6.41] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 10/03/2019] [Indexed: 12/24/2022] Open
Abstract
PURPOSE It is essential to have an appropriate measure to assess macular pigment (MP) that can provide an accurate, valid, and reliable representation of the MP within the macula. The aim of this study was to describe and introduce MP optical volume (MPOV) as an optimal value for reporting MP. METHODS Three hundred ninety-three subjects were analyzed using the Heidelberg Spectralis with the investigational MP optical density (MPOD) module to measure MPOV and MPOD at four foveal eccentricities (0.23°, 0.51°, 0.98°, 1.76° [7° as reference point]). Lutein (L) and zeaxanthin (Z) dietary intake and serum concentrations were evaluated. RESULTS MPOV mean was 5094 (95%CI, 4877-5310); range: 527 to 10,652. MPOV was inversely correlated with body mass index and positively correlated with education (r = -0.156, P = 0.002 and r = 0.124, P = 0.014, respectively). Serum concentrations of L and Z were positively correlated with MPOV (r = 0.422, P < 0.001 and r = 0.285, P < 0.001, respectively). MPOV was positively correlated to MPOD at all measured eccentricities, with the strongest agreement at 1.76° (r = 0.906, P < 0.001). Serum concentrations of L and Z, BMI, education, and age (P < 0.001) were found to be significant predictors of MPOV. CONCLUSIONS The Spectralis MPOV measurement provided a comprehensive and detailed evaluation of the MP profile. The Spectralis MPOV should be considered a preferred metric for the assessment of MP. TRANSLATIONAL RELEVANCE Applying a standardized method for the assessment and report of MP will allow to fully derive meaning from observational studies and to successfully implement this MP measurement technique in research and clinical settings.
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Affiliation(s)
- Marina Green-Gomez
- Nutrition Research Centre Ireland, School of Health Science, Carriganore House, Waterford Institute of Technology, West Campus, Waterford, Ireland
| | | | - Christine A. Curcio
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Rachel Moran
- Nutrition Research Centre Ireland, School of Health Science, Carriganore House, Waterford Institute of Technology, West Campus, Waterford, Ireland
| | - Warren Roche
- Nutrition Research Centre Ireland, School of Health Science, Carriganore House, Waterford Institute of Technology, West Campus, Waterford, Ireland
| | - John M. Nolan
- Nutrition Research Centre Ireland, School of Health Science, Carriganore House, Waterford Institute of Technology, West Campus, Waterford, Ireland
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A review of the putative causal mechanisms associated with lower macular pigment in diabetes mellitus. Nutr Res Rev 2019; 32:247-264. [PMID: 31409441 DOI: 10.1017/s095442241900012x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Macular pigment (MP) confers potent antioxidant and anti-inflammatory effects at the macula, and may therefore protect retinal tissue from the oxidative stress and inflammation associated with ocular disease and ageing. There is a body of evidence implicating oxidative damage and inflammation as underlying pathological processes in diabetic retinopathy. MP has therefore become a focus of research in diabetes, with recent evidence suggesting that individuals with diabetes, particularly type 2 diabetes, have lower MP relative to healthy controls. The present review explores the currently available evidence to illuminate the metabolic perturbations that may possibly be involved in MP's depletion. Metabolic co-morbidities commonly associated with type 2 diabetes, such as overweight/obesity, dyslipidaemia, hyperglycaemia and insulin resistance, may have related and independent relationships with MP. Increased adiposity and dyslipidaemia may adversely affect MP by compromising the availability, transport and assimilation of these dietary carotenoids in the retina. Furthermore, carotenoid intake may be compromised by the dietary deficiencies characteristic of type 2 diabetes, thereby further compromising redox homeostasis. Candidate causal mechanisms to explain the lower MP levels reported in diabetes include increased oxidative stress, inflammation, hyperglycaemia, insulin resistance, overweight/obesity and dyslipidaemia; factors that may negatively affect redox status, and the availability, transport and stabilisation of carotenoids in the retina. Further study in diabetic populations is warranted to fully elucidate these relationships.
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30
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Sahin K, Gencoglu H, Akdemir F, Orhan C, Tuzcu M, Sahin N, Yilmaz I, Juturu V. Lutein and zeaxanthin isomers may attenuate photo-oxidative retinal damage via modulation of G protein-coupled receptors and growth factors in rats. Biochem Biophys Res Commun 2019; 516:163-170. [PMID: 31204054 DOI: 10.1016/j.bbrc.2019.06.032] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 06/07/2019] [Indexed: 01/05/2023]
Abstract
BACKGROUND Retina photoreceptor cells are specially adapted for functioning over comprehensive ambient light conditions. Lutein and Zeaxanthin isomers (L/Zi) can protect photoreceptor cells against excessive light degeneration. Efficacy of L/Zi has been assessed on some G protein-coupled receptors (GPCRs), transcription and neurotrophic factors in the retina of rats exposed to incremental intense light emitting diode (LED) illumination conditions. METHODS Forty-two male rats (age: 8 weeks) were randomly assigned to six treatment groups, 7 rats each. The rats with a 3x2 factorial design were kept under 3 intense light conditions (12hL/12hD, 16hL/8hD, 24hL/0hD) and received two levels of L/Zi (0 or 100 mg/kg BW) for two months. Increased nuclear factor-kappa B (NF-κB), glial fibrillary acid protein (GFAP), and decreased Rhodopsin (Rho), Rod arrestin (Sag), G Protein Subunit Alpha Transducin1 (Gnat1), neural cell adhesion molecule (NCAM), growth-associated protein-43 (GAP43), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase 1 (HO-1) were observed in 24 h light intensity adaptation followed by 16 h IL and 8 h D. RESULTS L/Zi administration significantly improved antioxidant capacity and retinal Rho, Rod-arrestin (Sag), Gnat1, NCAM, GAP43, BDNF, NGF, IGF1, Nrf2, and HO-1 levels. However, the levels of NF-κB and GFAP levels were decreased by administration of L/Zi. CONCLUSIONS According to these results, L/Zi may be assumed as an adjunct therapy to prevent early photoreceptor cell degeneration and neutralize free radicals derived from oxidative stress.
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Affiliation(s)
- Kazim Sahin
- Department of Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey.
| | - Hasan Gencoglu
- Department of Biology, Faculty of Science, Firat University, Elazig, Turkey
| | - Fatih Akdemir
- Faculty of Fisheries, Inonu University, Malatya, Turkey
| | - Cemal Orhan
- Department of Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey
| | - Mehmet Tuzcu
- Department of Biology, Faculty of Science, Firat University, Elazig, Turkey
| | - Nurhan Sahin
- Department of Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey
| | - Ismet Yilmaz
- Department of Pharmacology, Faculty of Pharmacy, Inonu University, Malatya, Turkey
| | - Vijaya Juturu
- Research and Development, OmniActive Health Technologies Inc., Morristown, NJ, United States
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Rossino MG, Casini G. Nutraceuticals for the Treatment of Diabetic Retinopathy. Nutrients 2019; 11:nu11040771. [PMID: 30987058 PMCID: PMC6520779 DOI: 10.3390/nu11040771] [Citation(s) in RCA: 72] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 03/19/2019] [Accepted: 03/28/2019] [Indexed: 02/07/2023] Open
Abstract
Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus and is characterized by degeneration of retinal neurons and neoangiogenesis, causing a severe threat to vision. Nowadays, the principal treatment options for DR are laser photocoagulation, vitreoretinal surgery, or intravitreal injection of drugs targeting vascular endothelial growth factor. However, these treatments only act at advanced stages of DR, have short term efficacy, and cause side effects. Treatment with nutraceuticals (foods providing medical or health benefits) at early stages of DR may represent a reasonable alternative to act upstream of the disease, preventing its progression. In particular, in vitro and in vivo studies have revealed that a variety of nutraceuticals have significant antioxidant and anti-inflammatory properties that may inhibit the early diabetes-driven molecular mechanisms that induce DR, reducing both the neural and vascular damage typical of DR. Although most studies are limited to animal models and there is the problem of low bioavailability for many nutraceuticals, the use of these compounds may represent a natural alternative method to standard DR treatments.
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Affiliation(s)
| | - Giovanni Casini
- Department of Biology, University of Pisa, via San Zeno 31, 56127 Pisa, Italy.
- Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, 56124 Pisa, Italy.
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Steiner BM, McClements DJ, Davidov-Pardo G. Encapsulation systems for lutein: A review. Trends Food Sci Technol 2018. [DOI: 10.1016/j.tifs.2018.10.003] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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Macular Pigment Distribution as Prognostic Marker for Disease Progression in Macular Telangiectasia Type 2. Am J Ophthalmol 2018; 194:163-169. [PMID: 30053477 DOI: 10.1016/j.ajo.2018.07.017] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2018] [Revised: 07/12/2018] [Accepted: 07/15/2018] [Indexed: 11/20/2022]
Abstract
PURPOSE To evaluate macular pigment distribution pattern as a prognostic marker for disease progression in patients with macular telangiectasia type 2 (MacTel). DESIGN Retrospective cohort study. METHODS In this single-center study, 90 eyes of 47 patients were analyzed. Macular pigment optical density (MPOD) was measured with dual-wavelength fundus autofluorescence. Eyes were graded into MPOD distribution classes 1 to 3 with increasing loss of macular pigment and grading was performed masked by 2 independent graders. Best-corrected visual acuity, reading acuity, total scotoma size in fundus-controlled perimetry (microperimetry), and break of the ellipsoid zone (EZ) in optical coherence tomography (en face measurement) were defined as functional and morphologic outcome parameters and evaluated at baseline and after 60 months. RESULTS After a mean review period of 59.6 months (±standard deviation 5.2 months), no change between MPOD classes was observed compared to baseline. Morphologic and functional deficits were limited to the area of MPOD loss. At last follow-up, a significant mean decrease of visual acuity and reading acuity as well as a significant mean increase of scotoma size and EZ break were observed in eyes assigned to MPOD classes 2 and 3, while outcome parameters remained stable in eyes of class 1. CONCLUSIONS The results indicate that MPOD and its distribution may serve as a prognostic marker for disease progression and functional impairment in patients with MacTel.
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Kumari N, Cher J, Chua E, Hamzah H, Wong TY, Cheung CY. Association of serum lutein and zeaxanthin with quantitative measures of retinal vascular parameters. PLoS One 2018; 13:e0203868. [PMID: 30260964 PMCID: PMC6160008 DOI: 10.1371/journal.pone.0203868] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Accepted: 08/29/2018] [Indexed: 12/12/2022] Open
Abstract
To evaluate the association between serum carotenoids and quantitative measures of retinal vasculature in elderly Singapore Chinese subjects. The following details were collected in 128 healthy subjects: sociodemographics, lifestyle information, medical and drug history, and anthropometric measurements. Serum concentrations of carotenoids were estimated in fasting venous blood using high performance liquid chromatography. Retinal vascular parameters were quantitatively measured from retinal photographs using a computer-assisted program (Singapore I Vessel Assessment). The mean age of the population was 54.1 years (range 40 to 81 years). In multiple linear regression analysis, per SD decrease in retinal arteriolar caliber [β = 0.045 (0.003 to 0.086), p = 0.036], per SD increase in retinal venular caliber [β = -0.045 (-0.086 to -0.003), p = 0.036] and per SD increase in arteriolar branching angle [β = -0.039 (-0.072 to -0.006), p = 0.021] were associated with decreased serum lutein. Per SD increase in retinal venular tortuosity [β = -0.0075 (-0.0145 to -0.0004), p = 0.039] and per SD increase in arteriolar branching angle (β = -0.0073 [-0.0142 to -0.0059], p = 0.041) were associated with decreased serum zeaxanthin. None of the other carotenoids demonstrated meaningful relationship with quantitative measures of retinal vasculature. Lower levels of lutein and zeaxanthin demonstrated significant relationship with adverse quantitative measures of retinal vasculature in elderly healthy subjects.
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Affiliation(s)
- Neelam Kumari
- Department of Ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
- Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Republic of Singapore
- * E-mail:
| | - Joanna Cher
- Department of Ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore, Republic of Singapore
| | - Edwin Chua
- Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Republic of Singapore
| | - Haslina Hamzah
- Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Republic of Singapore
| | - Tien Yin Wong
- Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Republic of Singapore
- Ophthalmology and Visual Sciences Academic Clinical Programme, Duke-NUS Graduate Medical School, National University of Singapore, Singapore, Republic of Singapore
| | - Carol Y. Cheung
- Singapore Eye Research Institute, Singapore National Eye Center, Singapore, Republic of Singapore
- Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Shatin, Hong Kong, The People’s Republic of China
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Li S, Liu N, Lin L, Sun ED, Li JD, Li PK. Macular pigment and serum zeaxanthin levels with Goji berry supplement in early age-related macular degeneration. Int J Ophthalmol 2018; 11:970-975. [PMID: 29977809 DOI: 10.18240/ijo.2018.06.12] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 02/05/2018] [Indexed: 11/23/2022] Open
Abstract
AIM To evaluate the efficacy of Goji berry supplementation on improving macular pigment, serum zeaxanthin levels and visual acuity in patients with early age-related macular degeneration (AMD). METHODS A total of 114 patients (aged from 51 to 92y, mean age 69.53±8.41y) with early AMD were enrolled in our prospective, randomized controlled study. The included patients were assigned randomly to the Goji group (n=57) with 25 g of Goji berries supplementation per day for 90d and the control group (n=57) with their normal diet for 90d. Macular pigment optical density (MPOD) was measured using heterochromatic flicker photometry (HFP). The levels of serum lutein (L)/zeaxanthin (Z) were analyzed using high-performance liquid chromatography (HPLC). MPOD, serum L/Z levels and best corrected visual acuity (BCVA) were recorded at baseline and 90d. RESULTS In the Goji group, there were no statistically significant differences in the serum L levels between the baseline (0.199±0.149 µmol/mL) and 90d (0.203±0.181 µmol/mL) (t=-0.186, P=0.850); however the serum Z levels were increased at 90d (0.101±0.087 µmol/mL) compared with those at the baseline (0.029±0.032 µmol/mL) (t=6.412, P<0.001). Patients treated with Goji berry for 90d showed an elevated MPOD (0.877±0.202 DU) from the baseline (0.731±0.205 DU) (t=-4.741, P=0.000). In contrast to the control group, the serum Z levels and MPOD were higher in the Goji group at 90d (both P<0.05). At 90d, patients with Goji berry supplementation had a relative decrease in BCVA (0.21±0.18 logMAR) compared with the baseline (0.27±0.20) (t=2.397, P=0.020). CONCLUSION Overall, daily supplementation with Goji berry for 90d improves MPOD by increasing serum Z levels rather than serum L levels in early AMD patients. Goji berry may be an effective therapeutic intervention for preventing the progression of early AMD.
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Affiliation(s)
- Shang Li
- Department of Ophthalmology, Beijing YouAn Hospital, Capital Medical University Beijing, Beijing100069, China
| | - Na Liu
- Department of Ophthalmology, China Rehabilitation Research Center, Chinese Rehabilitation Science Institute, Capital Medical University, Beijing 100068, China
| | - Li Lin
- Research Center, Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing 100091, China
| | - Er-Dan Sun
- Department of Ophthalmology, China Rehabilitation Research Center, Chinese Rehabilitation Science Institute, Capital Medical University, Beijing 100068, China
| | - Jian-Da Li
- Department of Ophthalmology, China Rehabilitation Research Center, Chinese Rehabilitation Science Institute, Capital Medical University, Beijing 100068, China
| | - Peng-Kun Li
- Department of Ophthalmology, China Rehabilitation Research Center, Chinese Rehabilitation Science Institute, Capital Medical University, Beijing 100068, China
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Supplementation with macular carotenoids improves visual performance of transgenic mice. Arch Biochem Biophys 2018; 649:22-28. [PMID: 29742455 DOI: 10.1016/j.abb.2018.05.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Revised: 04/19/2018] [Accepted: 05/04/2018] [Indexed: 12/29/2022]
Abstract
Carotenoid supplementation can improve human visual performance, but there is still no validated rodent model to test their effects on visual function in laboratory animals. We recently showed that mice deficient in β-carotene oxygenase 2 (BCO2) and/or β-carotene oxygenase 1 (BCO1) enzymes can accumulate carotenoids in their retinas, allowing us to investigate the effects of carotenoids on the visual performance of mice. Using OptoMotry, a device to measure visual function in rodents, we examined the effect of zeaxanthin, lutein, and β-carotene on visual performance of various BCO knockout mice. We then transgenically expressed the human zeaxanthin-binding protein GSTP1 (hGSTP1) in the rods of bco2-/- mice to examine if delivering more zeaxanthin to retina will improve their visual function further. The visual performance of bco2-/- mice fed with zeaxanthin or lutein was significantly improved relative to control mice fed with placebo beadlets. β-Carotene had no significant effect in bco2-/- mice but modestly improved cone visual function of bco1-/- mice. Expression of hGSTP1 in the rods of bco2-/-mice resulted in a 40% increase of retinal zeaxanthin and further improvement of visual performance. This work demonstrates that these "macular pigment mice" may serve as animal models to study carotenoid function in the retina.
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Visual Function Metrics in Early and Intermediate Dry Age-related Macular Degeneration for Use as Clinical Trial Endpoints. Am J Ophthalmol 2018; 189:127-138. [PMID: 29477964 DOI: 10.1016/j.ajo.2018.02.012] [Citation(s) in RCA: 81] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 02/12/2018] [Accepted: 02/14/2018] [Indexed: 01/15/2023]
Abstract
PURPOSE To evaluate and quantify visual function metrics to be used as endpoints of age-related macular degeneration (AMD) stages and visual acuity (VA) loss in patients with early and intermediate AMD. DESIGN Cross-sectional analysis of baseline data from a prospective study. METHODS One hundred and one patients were enrolled at Duke Eye Center: 80 patients with early AMD (Age-Related Eye Disease Study [AREDS] stage 2 [n = 33] and intermediate stage 3 [n = 47]) and 21 age-matched, normal controls. A dilated retinal examination, macular pigment optical density measurements, and several functional assessments (best-corrected visual acuity, macular integrity assessment mesopic microperimety, dark adaptometry, low-luminance visual acuity [LLVA] [standard using a log 2.0 neutral density filter and computerized method], and cone contrast test [CCT]) were performed. Low-luminance deficit (LLD) was defined as the difference in numbers of letters read at standard vs low luminance. Group comparisons were performed to evaluate differences between the control and the early and intermediate AMD groups using 2-sided significance tests. RESULTS Functional measures that significantly distinguished between normal and intermediate AMD were standard and computerized (0.5 cd/m2) LLVA, percent reduced threshold and average threshold on microperimetry, CCTs, and rod intercept on dark adaptation (P < .05). The intermediate group demonstrated deficits in microperimetry reduced threshhold, computerized LLD2, and dark adaptation (P < .05) relative to early AMD. CONCLUSIONS Our study suggests that LLVA, microperimetry, CCT, and dark adaptation may serve as functional measures differentiating early-to-intermediate stages of dry AMD.
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Phelan D, Prado-Cabrero A, Nolan JM. Analysis of Lutein, Zeaxanthin, and Meso-Zeaxanthin in the Organs of Carotenoid-Supplemented Chickens. Foods 2018; 7:E20. [PMID: 29401639 PMCID: PMC5848124 DOI: 10.3390/foods7020020] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 01/29/2018] [Accepted: 01/30/2018] [Indexed: 11/18/2022] Open
Abstract
The macular carotenoids (i.e., lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ)) exhibit anti-inflammatory, antioxidant and optical properties that are believed to support human health and function. Studying the accumulation and distribution of these nutrients in tissues and organs, in addition to the eye, is an important step in understanding how these nutrients might support global human function and health (e.g., heart and brain). Chicken is an appropriate animal model with which to study the accumulation of these carotenoids in organs, as the relevant transport molecules and carotenoid binding proteins for L, Z and MZ are present in both humans and chickens. In this experiment, a sample of 3 chickens that were supplemented with L and MZ diacetate (active group) and a sample of 3 chickens that received a standard diet (control group) were analysed. Both groups were analysed for L, Z and MZ concentrations in the brain, eyes, heart, lung, duodenum/pancreas, jejunum/ileum, kidney and breast tissue. L, Z and MZ were identified in all the organs/tissues analysed from the active group. L and Z were identified in all of the organs/tissues analysed from the control group; while, MZ was identified in the eyes of these animals only. The discovery that MZ is accumulated in the tissues and organs of chickens supplemented with this carotenoid is important, given that it is known that a combination of L, Z and MZ exhibits superior antioxidant capacity when compared to any of these carotenoids in isolation.
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Affiliation(s)
- David Phelan
- Nutrition Research Centre Ireland, School of Health Science, Carriganore House, Waterford Institute of Technology, West Campus, Waterford X91 K236, Ireland.
| | - Alfonso Prado-Cabrero
- Nutrition Research Centre Ireland, School of Health Science, Carriganore House, Waterford Institute of Technology, West Campus, Waterford X91 K236, Ireland
| | - John M Nolan
- Nutrition Research Centre Ireland, School of Health Science, Carriganore House, Waterford Institute of Technology, West Campus, Waterford X91 K236, Ireland.
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Gong X, Draper CS, Allison GS, Marisiddaiah R, Rubin LP. Effects of the Macular Carotenoid Lutein in Human Retinal Pigment Epithelial Cells. Antioxidants (Basel) 2017; 6:antiox6040100. [PMID: 29207534 PMCID: PMC5745510 DOI: 10.3390/antiox6040100] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 11/30/2017] [Accepted: 12/01/2017] [Indexed: 12/16/2022] Open
Abstract
Retinal pigment epithelial (RPE) cells are central to retinal health and homoeostasis. Oxidative stress-induced damage to the RPE occurs as part of the pathogenesis of age-related macular degeneration and neovascular retinopathies (e.g., retinopathy of prematurity, diabetic retinopathy). The xanthophyll carotenoids, lutein and zeaxanthin, are selectively taken up by the RPE, preferentially accumulated in the human macula, and transferred to photoreceptors. These macular xanthophylls protect the macula (and the broader retina) via their antioxidant and photo-protective activities. This study was designed to investigate effects of various carotenoids (β-carotene, lycopene, and lutein) on RPE cells subjected to either hypoxia or oxidative stress, in order to determine if there is effect specificity for macular pigment carotenoids. Using human RPE-derived ARPE-19 cells as an in vitro model, we exposed RPE cells to various concentrations of the specific carotenoids, followed by either graded hypoxia or oxidative stress using tert-butyl hydroperoxide (tBHP). The results indicate that lutein and lycopene, but not β-carotene, inhibit cell growth in undifferentiated ARPE-19 cells. Moreover, cell viability was decreased under hypoxic conditions. Pre-incubation of ARPE-19 cells with lutein or lycopene protected against tBHP-induced cell loss and cell co-exposure of lutein or lycopene with tBHP essentially neutralized tBHP-dependent cell death at tBHP concentrations up to 500 μM. Our findings indicate that lutein and lycopene inhibit the growth of human RPE cells and protect the RPE against oxidative stress-induced cell loss. These findings contribute to the understanding of the protective mechanisms attributable to retinal xanthophylls in eye health and retinopathies.
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Affiliation(s)
- Xiaoming Gong
- Department of Pediatrics, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
| | - Christian S Draper
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
| | - Geoffrey S Allison
- Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
| | | | - Lewis P Rubin
- Department of Pediatrics, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
- Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
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Shyam R, Vachali P, Gorusupudi A, Nelson K, Bernstein PS. All three human scavenger receptor class B proteins can bind and transport all three macular xanthophyll carotenoids. Arch Biochem Biophys 2017; 634:21-28. [PMID: 28947101 PMCID: PMC5698089 DOI: 10.1016/j.abb.2017.09.013] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Revised: 09/15/2017] [Accepted: 09/20/2017] [Indexed: 12/13/2022]
Abstract
Carotenoids are plant pigment molecules that are potent antioxidants. Carotenoids cannot be synthesized de novo; therefore, their dietary intake and transport to various tissues are essential to harness their health benefits. Two of the three scavenger receptor class B (SRB) proteins, SR-B1 and CD36, have been implicated as carotenoid transporters in lower species and in various tissues of higher animals. The function of the third SRB protein, SR-B2, in carotenoid transport is unknown. Using surface plasmon resonance (SPR) analyses, we have determined that all three human SRB proteins are capable of binding the macular xanthophyll carotenoids; lutein, zeaxanthin, and meso-zeaxanthin. By over-expressing human SRB proteins in cells that do not endogenously express SRBs, we have determined that lutein uptake is enhanced in the presence of LDL and is mediated by SR-B1 and CD36. SR-B1, SR-B2, and CD36 were able to take up significant amounts of zeaxanthin as well as meso-zeaxanthin, and uptake was increased in the presence of HDL. Our analyses revealed no apparent differences in protein expression profiles of SRBs in central and peripheral regions of human donor tissues, indicating that carotenoid-binding proteins rather than transporters are likely to mediate selective accumulation of carotenoids into the macula.
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Affiliation(s)
- Rajalekshmy Shyam
- Department of Ophthalmology and Visual Sciences, University of Utah, 65 N Mario Capecchi Dr, Salt Lake City, UT, United States; Department of Neurobiology and Anatomy, University of Utah, 20 S 2030 E, Salt Lake City, UT, United States
| | - Preejith Vachali
- Department of Ophthalmology and Visual Sciences, University of Utah, 65 N Mario Capecchi Dr, Salt Lake City, UT, United States
| | - Aruna Gorusupudi
- Department of Ophthalmology and Visual Sciences, University of Utah, 65 N Mario Capecchi Dr, Salt Lake City, UT, United States
| | - Kelly Nelson
- Department of Ophthalmology and Visual Sciences, University of Utah, 65 N Mario Capecchi Dr, Salt Lake City, UT, United States
| | - Paul S Bernstein
- Department of Ophthalmology and Visual Sciences, University of Utah, 65 N Mario Capecchi Dr, Salt Lake City, UT, United States; Department of Neurobiology and Anatomy, University of Utah, 20 S 2030 E, Salt Lake City, UT, United States.
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Stability of Commercially Available Macular Carotenoid Supplements in Oil and Powder Formulations. Nutrients 2017; 9:nu9101133. [PMID: 29039801 PMCID: PMC5691749 DOI: 10.3390/nu9101133] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Revised: 10/03/2017] [Accepted: 10/13/2017] [Indexed: 11/23/2022] Open
Abstract
We previously identified that the concentration of zeaxanthin in some commercially available carotenoid supplements did not agree with the product’s label claim. The conclusion of this previous work was that more quality assurance was needed to guarantee concordance between actual and declared concentrations of these nutrients i.e., lutein (L) zeaxanthin (Z) and meso-zeaxanthin (MZ) in commercially available supplements. Since this publication, we performed further analyses using different commercially available macular carotenoid supplements. Three capsules from one batch of eight products were analysed at two different time points. The results have been alarming. All of the powder filled products (n = 3) analysed failed to comply with their label claim (L: 19–74%; Z: 57–73%; MZ: 83–97%); however, the oil filled soft gel products (n = 5) met or were above their label claim (L: 98–122%; Z: 117–162%; MZ: 97–319%). We also identified that the carotenoid content of the oil filled capsules were stable over time (e.g., L average percentage change: −1.7%), but the powder filled supplements degraded over time (e.g., L average percentage change: −17.2%). These data are consistent with our previous work, and emphasize the importance of using carotenoid interventions in oil based formulas rather than powder filled formulas.
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RPE65 has an additional function as the lutein to meso-zeaxanthin isomerase in the vertebrate eye. Proc Natl Acad Sci U S A 2017; 114:10882-10887. [PMID: 28874556 DOI: 10.1073/pnas.1706332114] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Carotenoids are plant-derived pigment molecules that vertebrates cannot synthesize de novo that protect the fovea of the primate retina from oxidative stress and light damage. meso-Zeaxanthin is an ocular-specific carotenoid for which there are no common dietary sources. It is one of the three major carotenoids present at the foveal center, but the mechanism by which it is produced in the eye is unknown. An isomerase enzyme is thought to be responsible for the transformation of lutein to meso-zeaxanthin by a double-bond shift mechanism, but its identity has been elusive. We previously found that meso-zeaxanthin is produced in a developmentally regulated manner in chicken embryonic retinal pigment epithelium (RPE)/choroid in the absence of light. In the present study, we show that RPE65, the isomerohydrolase enzyme of the vertebrate visual cycle that catalyzes the isomerization of all-trans-retinyl esters to 11-cis-retinol, is also the isomerase enzyme responsible for the production of meso-zeaxanthin in vertebrates. Its RNA is up-regulated 23-fold at the time of meso-zeaxanthin production during chicken eye development, and we present evidence that overexpression of either chicken or human RPE65 in cell culture leads to the production of meso-zeaxanthin from lutein. Pharmacologic inhibition of RPE65 function resulted in significant inhibition of meso-zeaxanthin biosynthesis during chicken eye development. Structural docking experiments revealed that the epsilon ring of lutein fits into the active site of RPE65 close to the nonheme iron center. This report describes a previously unrecognized additional activity of RPE65 in ocular carotenoid metabolism.
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Health Effects of Carotenoids during Pregnancy and Lactation. Nutrients 2017; 9:nu9080838. [PMID: 28777356 PMCID: PMC5579631 DOI: 10.3390/nu9080838] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Revised: 07/31/2017] [Accepted: 08/01/2017] [Indexed: 02/07/2023] Open
Abstract
Adequate nutrition is particularly important during pregnancy since it is needed not only for maintaining the health of the mother, but also determines the course of pregnancy and its outcome, fetus development as well as the child’s health after birth and during the later period of life. Data coming from epidemiological and interventions studies support the observation that carotenoids intake provide positive health effects in adults and the elderly population. These health effects are the result of their antioxidant and anti-inflammatory properties. Recent studies have also demonstrated the significant role of carotenoids during pregnancy and infancy. Some studies indicate a correlation between carotenoid status and lower risk of pregnancy pathologies induced by intensified oxidative stress, but results of these investigations are equivocal. Carotenoids have been well studied in relation to their beneficial role in the prevention of preeclampsia. It is currently hypothesized that carotenoids can play an important role in the prevention of preterm birth and intrauterine growth restriction. Carotenoid status in the newborn depends on the nutritional status of the mother, but little is known about the transfer of carotenoids from the mother to the fetus. Carotenoids are among the few nutrients found in breast milk, in which the levels are determined by the mother’s diet. Nutritional status of the newborn directly depends on its diet. Both mix feeding and artificial feeding may cause depletion of carotenoids since infant formulas contain only trace amounts of these compounds. Carotenoids, particularly lutein and zeaxanthin play a significant role in the development of vision and nervous system (among others, they are important for the development of retina as well as energy metabolism and brain electrical activity). Furthermore, more scientific evidence is emerging on the role of carotenoids in the prevention of disorders affecting preterm infants, who are susceptible to oxidative stress, particularly retinopathy of prematurity.
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Natesan S, Krishnaswami V, Ponnusamy C, Madiyalakan M, Woo T, Palanisamy R. Hypocrellin B and nano silver loaded polymeric nanoparticles: Enhanced generation of singlet oxygen for improved photodynamic therapy. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2017; 77:935-946. [PMID: 28532114 DOI: 10.1016/j.msec.2017.03.179] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/06/2016] [Revised: 01/19/2017] [Accepted: 03/21/2017] [Indexed: 12/21/2022]
Abstract
A nanoparticulate photodynamic approach was employed with an objective to achieve enhanced production of singlet oxygen (1O2), for the management of posterior segment eye diseases like age related macular degeneration. The hypocrellin B (HB) loaded poly lactide-co-glycolide nanoparticle formulations were incorporated with nano silver (HBS-NPs). The optimized HBS-NPs contained 2.60±0.06mg/mL of HB and showed (i) 135.6 to 828.2nm size range, and (ii) negative zeta potential with a narrow polydispersity index. The DSC thermograms suggested the amorphous nature of HB inside the HBS-NPs. With the average encapsulation efficiency of 92.9±1.79%, the drug release from the HBS-NPs followed a biphasic pattern with an initial burst of 3.50% during first 8h followed by a sustained release of 47.82% within 3days. The interaction between nano silver and HB as assessed by the increase in spectral intensity of Raman spectrum demonstrates that HB may be attached over the nano silver. Generation of reactive oxygen species (ROS) by HBS-NPs was significantly higher than that of HB/HB-NPs. The singlet oxygen generating efficiency assessed using EPR spectrometer follows the order of nano silver>HB-NPs>pure HB drug solution>HBS-NPs. The HBS-NPs had a concentration and time dependent phototoxicity on A549 (human adeno lung carcinoma) cells in the presence of light providing a superior phototoxic effect (82.2% at 50μM) at 2h irradiation. The CAM treated with HBS-NPs showed a significant anti-angiogenic effect compared to a blank formulation. In vivo biodistribution studies revealed that intravenous administration of HBS-NPs lead into significant exposure to the posterior segment of the eye. This proof of principle study demonstrates that HB based nanoparticles may be a valuable new tool for application in ocular photodynamic therapy for the treatment of AMD in future.
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Affiliation(s)
- Subramanian Natesan
- Laboratory for Lipid Based Systems, Department of Pharmaceutical Technology, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, Tamilnadu, India.
| | - Venkateshwaran Krishnaswami
- Laboratory for Lipid Based Systems, Department of Pharmaceutical Technology, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, Tamilnadu, India
| | - Chandrasekar Ponnusamy
- Laboratory for Lipid Based Systems, Department of Pharmaceutical Technology, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, Tamilnadu, India
| | | | | | - Rajaguru Palanisamy
- Department of Biotechnology, Bharathidasan Institute of Technology, Anna University, Tiruchirappalli, Tamilnadu, India
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Retinal accumulation of zeaxanthin, lutein, and β-carotene in mice deficient in carotenoid cleavage enzymes. Exp Eye Res 2017; 159:123-131. [PMID: 28286282 DOI: 10.1016/j.exer.2017.02.016] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 12/29/2016] [Accepted: 02/28/2017] [Indexed: 12/11/2022]
Abstract
Carotenoid supplementation can prevent and reduce the risk of age-related macular degeneration (AMD) and other ocular disease, but until now, there has been no validated and well-characterized mouse model which can be employed to investigate the protective mechanism and relevant metabolism of retinal carotenoids. β-Carotene oxygenases 1 and 2 (BCO1 and BCO2) are the only two carotenoid cleavage enzymes found in animals. Mutations of the bco2 gene may cause accumulation of xanthophyll carotenoids in animal tissues, and BCO1 is involved in regulation of the intestinal absorption of carotenoids. To determine whether or not mice deficient in BCO1 and/or BCO2 can serve as a macular pigment mouse model, we investigated the retinal accumulation of carotenoids in these mice when fed with zeaxanthin, lutein, or β-carotene using an optimized carotenoid feeding method. HPLC analysis revealed that all three carotenoids were detected in sera, livers, retinal pigment epithelium (RPE)/choroids, and retinas of all of the mice, except that no carotenoid was detectable in the retinas of wild type (WT) mice. Significantly higher amounts of zeaxanthin and lutein accumulated in the retinas of BCO2 knockout (bco2-/-) mice and BCO1/BCO2 double knockout (bco1-/-/bco2-/-) mice relative to BCO1 knockout (bco1-/-) mice, while bco1-/- mice preferred to take up β-carotene. The levels of zeaxanthin and lutein were higher than β-carotene levels in the bco1-/-/bco2-/- retina, consistent with preferential uptake of xanthophyll carotenoids by retina. Oxidative metabolites were detected in mice fed with lutein or zeaxanthin but not in mice fed with β-carotene. These results indicate that bco2-/- and bco1-/-/bco2-/- mice could serve as reasonable non-primate models for macular pigment function in the vertebrate eye, while bco1-/- mice may be more useful for studies related to β-carotene.
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Neelam K, Goenadi CJ, Lun K, Yip CC, Au Eong KG. Putative protective role of lutein and zeaxanthin in diabetic retinopathy. Br J Ophthalmol 2017; 101:551-558. [PMID: 28232380 DOI: 10.1136/bjophthalmol-2016-309814] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Revised: 12/21/2016] [Accepted: 01/21/2017] [Indexed: 01/02/2023]
Abstract
Diabetic retinopathy (DR) is one of the most important microvascular complications of diabetes and remains the leading cause of blindness in the working-age individuals. The exact aetiopathogenesis of DR remains elusive despite major advances in basic science and clinical research. Oxidative damage as one of the underlying causes for DR is increasingly being recognised. In humans, three hydroxycarotenoids, lutein (L), zeaxanthin (Z) and meso-zeaxanthin (MZ), accumulate at the central retina (to the exclusion of all other dietary carotenoids), where they are collectively known as macular pigment. These hydroxycarotenoids by nature of their biochemical structure and function help neutralise reactive oxygen species, and thereby, prevent oxidative damage to the retina (biological antioxidants). Apart from their key antioxidant function, evidence is emerging that these carotenoids may also exhibit neuroprotective and anti-inflammatory function in the retina. Since the preliminary identification of hydroxycarotenoid in the human macula by Wald in the 1940s, there has been astounding progress in our knowledge of the role of these carotenoids in promoting ocular health. While the Age-Related Eye Disease Study 2 has established a clinical benefit for L and Z supplements in patients with age-related macular degeneration, the role of these carotenoids in other retinal diseases potentially linked to oxidative damage remains unclear. In this article, we comprehensively review the literature germane to the putative protective role of two hydroxycarotenoids, L and Z, in the pathogenesis of DR.
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Affiliation(s)
- Kumari Neelam
- Department of Ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore, Singapore.,Singapore Eye Research Institute, Singapore, Singapore
| | - Catherina J Goenadi
- Department of Ophthalmology, National University Hospital, Singapore, Singapore
| | - Katherine Lun
- Department of Ophthalmology, National University Hospital, Singapore, Singapore
| | - Chee Chew Yip
- Department of Ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore, Singapore
| | - Kah-Guan Au Eong
- Department of Ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore, Singapore.,Singapore International Eye Cataract Retina Centre, Mount Elizabeth Medical Centre, Singapore, Singapore.,International Eye Cataract Retina Centre, Farrer Park Medical Centre, Singapore, Singapore
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Zaheer K. Hen egg carotenoids (lutein and zeaxanthin) and nutritional impacts on human health: a review. CYTA - JOURNAL OF FOOD 2017. [DOI: 10.1080/19476337.2016.1266033] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- K. Zaheer
- Health and Nutrition, Toronto, ON, Canada
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49
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Serum and macular response to carotenoid-enriched egg supplementation in human subjects: the Egg Xanthophyll Intervention clinical Trial (EXIT). Br J Nutr 2017; 117:108-123. [PMID: 28122649 PMCID: PMC5297582 DOI: 10.1017/s0007114516003895] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The macular carotenoids lutein (L), zeaxanthin (Z) and meso-zeaxanthin
(MZ) accumulate at the macula, where they are collectively referred to as macular pigment
(MP). Augmentation of this pigment, typically achieved through diet and supplementation,
enhances visual function and protects against progression of age-related macular
degeneration. However, it is known that eggs are a rich dietary source of L and Z, in a
highly bioavailable matrix. In this single-blind placebo-controlled study, L- and
MZ-enriched eggs and control non-enriched eggs were fed to human subjects (mean age 41 and
35 years, respectively) over an 8-week period, and outcome measures included MP, visual
function and serum concentrations of carotenoids and cholesterol. Serum carotenoid
concentrations increased significantly in control and enriched egg groups, but to a
significantly greater extent in the enriched egg group (P<0·001
for L, Z and MZ). There was no significant increase in MP in either study group post
intervention, and we saw no significant improvement in visual performance in either group.
Total cholesterol increased significantly in each group, but it did not exceed the upper
limit of the normative range (6·5 mmol/l). Therefore, carotenoid-enriched eggs may
represent an effective dietary source of L, Z and MZ, reflected in significantly raised
serum concentrations of these carotenoids, and consequentially improved bioavailability
for capture by target tissues. However, benefits in terms of MP augmentation and /or
improved visual performance were not realised over the 8-week study period, and a study of
greater duration will be required to address these questions.
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Wakagi M, Watanabe J, Takahashi S, Yasui A, Takano-Ishikawa Y. Inter-laboratory Validation Study of a Singlet Oxygen Absorption Capacity Assay Method for Determining the Antioxidant Capacities of Antioxidant Solutions and Food Extracts. FOOD SCIENCE AND TECHNOLOGY RESEARCH 2017. [DOI: 10.3136/fstr.23.481] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
- Manabu Wakagi
- National Agriculture and Food Research Organization, National Food Research Institute
| | - Jun Watanabe
- National Agriculture and Food Research Organization, National Food Research Institute
| | | | - Akemi Yasui
- National Agriculture and Food Research Organization, National Food Research Institute
| | - Yuko Takano-Ishikawa
- National Agriculture and Food Research Organization, National Food Research Institute
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