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Burggraaf-Sánchez de las Matas R, Torres-Cuevas I, Millán I, Desco MDC, Oblaré-Delgado C, Asensi M, Mena-Mollá S, Oger C, Galano JM, Durand T, Ortega ÁL. Potential of Pterostilbene as an Antioxidant Therapy for Delaying Retinal Damage in Diabetic Retinopathy. Antioxidants (Basel) 2025; 14:244. [PMID: 40227230 PMCID: PMC11939822 DOI: 10.3390/antiox14030244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/15/2025] [Accepted: 01/21/2025] [Indexed: 04/15/2025] Open
Abstract
Chronic hyperglycemia is a major driver of neurovascular damage in diabetic retinopathy (DR), a leading cause of preventable blindness in adults. DR progression is often undetected until its advanced stages, with oxidative stress recognized as a primary contributor. In diabetes, oxidative stress disrupts retinal cellular balance, damaging proteins, DNA, and lipids, and triggering photoreceptor degeneration. Pterostilbene (Pter), a polyphenol with antioxidant properties, has demonstrated protective effects in DR animal models and was assessed in a pilot clinical study. DR patients treated with 250 mg/day of oral Pter showed a reduction in the development of retinal vascular alterations characteristic of the disease. Urinary analyses confirmed Pter's role in reducing the lipid peroxidation of polyunsaturated fatty acids (PUFAs), including arachidonic and adrenic acids, indicators of oxidative damage in DR. Pter also improved the GSH/GSSG ratio, reflecting a restored redox balance. However, after six months without treatment, retinal damage indicators reappeared, highlighting the importance of sustained intervention. These findings suggest that Pter may help slow the progression of DR by protecting against oxidative stress and highlight the importance of implementing antioxidant therapies from the diagnosis of diabetes, although its long-term impact and the development of consistent biomarkers deserve more research to optimize DR management.
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Affiliation(s)
| | - Isabel Torres-Cuevas
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Vicente Andrés Estellés Av. s/n, 46100 Burjassot, Spain; (I.T.-C.); (C.O.-D.); (M.A.); (S.M.-M.)
| | - Iván Millán
- Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Catedrático José Beltrán Martínez st, 46980 Paterna, Spain;
| | - María del Carmen Desco
- Vitreo-Retina Unit, Fundación de Oftalmología Médica de la Comunidad Valenciana (FOM), Pío Baroja st 12, 46015 Valencia, Spain;
- Department of Medicine and Surgery, Faculty of Health sciences, Universidad CEU Cardenal Herrera, Luis Vives st 1, 46115 Alfara del Patriarca, Spain
| | - Candela Oblaré-Delgado
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Vicente Andrés Estellés Av. s/n, 46100 Burjassot, Spain; (I.T.-C.); (C.O.-D.); (M.A.); (S.M.-M.)
| | - Miguel Asensi
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Vicente Andrés Estellés Av. s/n, 46100 Burjassot, Spain; (I.T.-C.); (C.O.-D.); (M.A.); (S.M.-M.)
| | - Salvador Mena-Mollá
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Vicente Andrés Estellés Av. s/n, 46100 Burjassot, Spain; (I.T.-C.); (C.O.-D.); (M.A.); (S.M.-M.)
| | - Camille Oger
- Institut des Biomolécules Max Mousseron (IBMM), Pôle Chimie Balard Recherche, UMR 5247, Université de Montpellier, CNRS, ENSCM, 340093 Montpellier, France; (C.O.); (J.-M.G.); (T.D.)
| | - Jean-Marie Galano
- Institut des Biomolécules Max Mousseron (IBMM), Pôle Chimie Balard Recherche, UMR 5247, Université de Montpellier, CNRS, ENSCM, 340093 Montpellier, France; (C.O.); (J.-M.G.); (T.D.)
| | - Thierry Durand
- Institut des Biomolécules Max Mousseron (IBMM), Pôle Chimie Balard Recherche, UMR 5247, Université de Montpellier, CNRS, ENSCM, 340093 Montpellier, France; (C.O.); (J.-M.G.); (T.D.)
| | - Ángel Luis Ortega
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Vicente Andrés Estellés Av. s/n, 46100 Burjassot, Spain; (I.T.-C.); (C.O.-D.); (M.A.); (S.M.-M.)
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Moldovan M, Capraș RD, Paşcalău R, Filip GA. Molecular Findings Before Vision Loss in the Streptozotocin-Induced Rat Model of Diabetic Retinopathy. Curr Issues Mol Biol 2025; 47:28. [PMID: 39852143 PMCID: PMC11763991 DOI: 10.3390/cimb47010028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 12/30/2024] [Accepted: 01/02/2025] [Indexed: 01/26/2025] Open
Abstract
The streptozotocin-induced rat model of diabetic retinopathy presents similarities to the disease observed in humans. After four weeks following the induction of diabetes, the rats experience vision impairment. During this crucial four-week period, significant changes occur, with vascular damage standing out as a clinically significant factor, alongside neovascularization. While redox imbalance, activation of microglia, secretion of pro-inflammatory cytokines, and neuronal cell death are also observed, the latter remains an emerging hypothesis requiring further exploration. This review is a comprehensive and up-to-date chronological depiction of the progression of diabetic retinopathy within the initial four weeks of hyperglycemia, which precede the onset of vision loss. The data are structured in weekly changes. In the first week, oxidative stress triggers the activation of retinal microglia, which produces inflammation, leading to altered neurotransmission. The second week is characterized by leukostasis, which promotes ischemia, while neural degeneration begins and is accompanied by a simultaneous increase in vessel permeability. The progression of redox and inflammatory imbalances characterized the third week. Finally, in the fourth week, significant developments occur as vessels dilate and become tortuous, neovascularization develops, and retinal thickness diminishes, ultimately leading to vision loss. Through this clearly structured outline, this review aims to delineate a framework for the progression of streptozotocin-induced diabetic retinopathy.
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Affiliation(s)
- Mădălina Moldovan
- Department of Anatomy and Embryology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (M.M.)
| | - Roxana-Denisa Capraș
- Department of Anatomy and Embryology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (M.M.)
| | - Raluca Paşcalău
- Ophthalmology Clinic, Cluj County Emergency Hospital, 400006 Cluj-Napoca, Romania
- Research and Development Institute, Transilvania University of Brasov, 500484 Brasov, Romania
| | - Gabriela Adriana Filip
- Department of Anatomy and Embryology, Iuliu Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (M.M.)
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Sbai O, Torrisi F, Fabrizio FP, Rabbeni G, Perrone L. Effect of the Mediterranean Diet (MeDi) on the Progression of Retinal Disease: A Narrative Review. Nutrients 2024; 16:3169. [PMID: 39339769 PMCID: PMC11434766 DOI: 10.3390/nu16183169] [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: 08/13/2024] [Revised: 09/10/2024] [Accepted: 09/11/2024] [Indexed: 09/30/2024] Open
Abstract
Worldwide, the number of individuals suffering from visual impairment, as well as those affected by blindness, is about 600 million and it will further increase in the coming decades. These diseases also seriously affect the quality of life in working-age individuals. Beyond the characterization of metabolic, genetic, and environmental factors related to ocular pathologies, it is important to verify how lifestyle may participate in the induction of the molecular pathways underlying these diseases. On the other hand, scientific studies are also contributing to investigations as to whether lifestyle could intervene in modulating pathophysiological cellular responses, including the production of metabolites and neurohormonal factors, through the intake of natural compounds capable of interfering with molecular mechanisms that lead to ocular diseases. Nutraceuticals are promising in ameliorating pathophysiological complications of ocular disease such as inflammation and neurodegeneration. Moreover, it is important to characterize the nutritional patterns and/or natural compounds that may be beneficial against certain ocular diseases. The adherence to the Mediterranean diet (MeDi) is proposed as a promising intervention for the prevention and amelioration of several eye diseases. Several characteristic compounds and micronutrients of MeDi, including vitamins, carotenoids, flavonoids, and omega-3 fatty acids, are proposed as adjuvants against several ocular diseases. In this review, we focus on studies that analyze the effects of MeDi in ameliorating diabetic retinopathy, macular degeneration, and glaucoma. The analysis of knowledge in this field is requested in order to provide direction on recommendations for nutritional interventions aimed to prevent and ameliorate ocular diseases.
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Affiliation(s)
- Oualid Sbai
- Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), LR11IPT02, Institut Pasteur de Tunis, Tunis 1068, Tunisia
| | - Filippo Torrisi
- Faculty of Medicine and Surgery, University KORE of Enna, 94100 Enna, Italy
| | | | - Graziella Rabbeni
- Faculty of Medicine and Surgery, University KORE of Enna, 94100 Enna, Italy
| | - Lorena Perrone
- Faculty of Medicine and Surgery, University KORE of Enna, 94100 Enna, Italy
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Serikbaeva A, Li Y, Ma S, Yi D, Kazlauskas A. Resilience to diabetic retinopathy. Prog Retin Eye Res 2024; 101:101271. [PMID: 38740254 PMCID: PMC11262066 DOI: 10.1016/j.preteyeres.2024.101271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 05/03/2024] [Accepted: 05/10/2024] [Indexed: 05/16/2024]
Abstract
Chronic elevation of blood glucose at first causes relatively minor changes to the neural and vascular components of the retina. As the duration of hyperglycemia persists, the nature and extent of damage increases and becomes readily detectable. While this second, overt manifestation of diabetic retinopathy (DR) has been studied extensively, what prevents maximal damage from the very start of hyperglycemia remains largely unexplored. Recent studies indicate that diabetes (DM) engages mitochondria-based defense during the retinopathy-resistant phase, and thereby enables the retina to remain healthy in the face of hyperglycemia. Such resilience is transient, and its deterioration results in progressive accumulation of retinal damage. The concepts that co-emerge with these discoveries set the stage for novel intellectual and therapeutic opportunities within the DR field. Identification of biomarkers and mediators of protection from DM-mediated damage will enable development of resilience-based therapies that will indefinitely delay the onset of DR.
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Affiliation(s)
- Anara Serikbaeva
- Department of Physiology and Biophysics, University of Illinois at Chicago, 1905 W Taylor St, Chicago, IL 60612, USA
| | - Yanliang Li
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1905 W Taylor St, Chicago, IL 60612, USA
| | - Simon Ma
- Department of Bioengineering, University of Illinois at Chicago, 1905 W Taylor St, Chicago, IL 60612, USA
| | - Darvin Yi
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1905 W Taylor St, Chicago, IL 60612, USA; Department of Bioengineering, University of Illinois at Chicago, 1905 W Taylor St, Chicago, IL 60612, USA
| | - Andrius Kazlauskas
- Department of Physiology and Biophysics, University of Illinois at Chicago, 1905 W Taylor St, Chicago, IL 60612, USA; Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1905 W Taylor St, Chicago, IL 60612, USA.
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5
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Tang Q, Buonfiglio F, Böhm EW, Zhang L, Pfeiffer N, Korb CA, Gericke A. Diabetic Retinopathy: New Treatment Approaches Targeting Redox and Immune Mechanisms. Antioxidants (Basel) 2024; 13:594. [PMID: 38790699 PMCID: PMC11117924 DOI: 10.3390/antiox13050594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 05/06/2024] [Accepted: 05/09/2024] [Indexed: 05/26/2024] Open
Abstract
Diabetic retinopathy (DR) represents a severe complication of diabetes mellitus, characterized by irreversible visual impairment resulting from microvascular abnormalities. Since the global prevalence of diabetes continues to escalate, DR has emerged as a prominent area of research interest. The development and progression of DR encompass a complex interplay of pathological and physiological mechanisms, such as high glucose-induced oxidative stress, immune responses, vascular endothelial dysfunction, as well as damage to retinal neurons. Recent years have unveiled the involvement of genomic and epigenetic factors in the formation of DR mechanisms. At present, extensive research explores the potential of biomarkers such as cytokines, molecular and cell therapies, antioxidant interventions, and gene therapy for DR treatment. Notably, certain drugs, such as anti-VEGF agents, antioxidants, inhibitors of inflammatory responses, and protein kinase C (PKC)-β inhibitors, have demonstrated promising outcomes in clinical trials. Within this context, this review article aims to introduce the recent molecular research on DR and highlight the current progress in the field, with a particular focus on the emerging and experimental treatment strategies targeting the immune and redox signaling pathways.
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Affiliation(s)
- Qi Tang
- Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany; (F.B.); (E.W.B.); (L.Z.); (N.P.); (C.A.K.)
| | | | | | | | | | | | - Adrian Gericke
- Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany; (F.B.); (E.W.B.); (L.Z.); (N.P.); (C.A.K.)
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Reyes-Goya C, Santana-Garrido Á, Espinosa-Martín P, Vázquez CM, Mate A. Wild and cultivated olive trees: Nutraceutical insights of extra virgin olive oils in cardiovascular and ocular diseases. Biochim Biophys Acta Mol Basis Dis 2024; 1870:166904. [PMID: 37793462 DOI: 10.1016/j.bbadis.2023.166904] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 09/22/2023] [Accepted: 09/26/2023] [Indexed: 10/06/2023]
Abstract
Extra virgin olive oil (EVOO) from Olea europaea (cultivated olive tree) and the oil obtained from the wild olive variety or acebuche (ACE oil from Olea oleaster) contain an extraordinary number of bioactive molecules. These include oleic acid, sterols, tocopherols, triterpene compounds, and polyphenols. Both oils are known for their healthy properties and are considered to be a nutraceutical tool against cardiovascular diseases, including arterial hypertension, preeclampsia, and ocular diseases such as glaucoma or diabetic retinopathy. The benefits of EVOO and ACE oil stem from their anti-inflammatory, antioxidant, and anti-cancer properties. They also have potential as prebiotic compounds. In this update, we synthesise and illustrate the various characteristics and beneficial effects of olive oils from different varieties of olive trees, with special emphasis on Olea oleaster, also known as Olea europaea, L. var. sylvestris.
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Affiliation(s)
- C Reyes-Goya
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Epidemiología Clínica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, 41013 Sevilla, Spain.
| | - Á Santana-Garrido
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Epidemiología Clínica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, 41013 Sevilla, Spain
| | - P Espinosa-Martín
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain
| | - C M Vázquez
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Epidemiología Clínica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, 41013 Sevilla, Spain.
| | - A Mate
- Departamento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain; Epidemiología Clínica y Riesgo Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, 41013 Sevilla, Spain
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Biswas A, Choudhury AD, Agrawal S, Bisen AC, Sanap SN, Verma SK, Kumar M, Mishra A, Kumar S, Chauhan M, Bhatta RS. Recent Insights into the Etiopathogenesis of Diabetic Retinopathy and Its Management. J Ocul Pharmacol Ther 2024; 40:13-33. [PMID: 37733327 DOI: 10.1089/jop.2023.0068] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/22/2023] Open
Abstract
Purpose: Diabetic retinopathy (DR) is a microvascular retinal disease associated with chronic diabetes mellitus, characterized by the damage of blood vessels in the eye. It is projected to become the leading cause of blindness, given the increasing burden of the diabetic population worldwide. The diagnosis and management of DR pose significant challenges for physicians because of the involvement of multiple biochemical pathways and the complexity of ocular tissues. This review aims to provide a comprehensive understanding of the molecular pathways implicated in the pathogenesis of DR, including the polyo pathway, hexosamine pathway, protein kinase C (PKC), JAK/STAT signaling pathways, and the renin-angiotensin system (RAS). Methods: Academic databases such as PubMed, Scopus, Google Scholar and Web of Science was systematically searched using a carefully constructed search strategy incorporating keywords like "Diabetic Retinopathy," "Molecular Pathways," "Pharmacological Treatments," and "Clinical Trials" to identify relevant literature for the comprehensive review. Results: In addition to activating other inflammatory cascades, these pathways contribute to the generation of oxidative stress within the retina. Furthermore, it aims to explore the existing pharmacotherapy options available for the treatment of DR. In addition to conventional pharmacological therapies such as corticosteroids, antivascular endothelial growth factors, and nonsteroidal anti-inflammatory drugs (NSAIDs), this review highlights the potential of repurposed drugs, phyto-pharmaceuticals, and novel pipeline drugs currently undergoing various stages of clinical trials. Conclusion: Overall, this review serves as a technical exploration of the complex nature of DR, highlighting both established and emerging molecular pathways implicated in its pathogenesis. Furthermore, it delves into the available pharmacological treatments, as well as the promising repurposed drugs, phyto-pharmaceuticals, and novel drugs currently being evaluated in clinical trials, with a focus on their specific mechanisms of action.
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Affiliation(s)
- Arpon Biswas
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Jawaharlal Nehru University, New Delhi, India
| | - Abhijit Deb Choudhury
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Jawaharlal Nehru University, New Delhi, India
| | - Sristi Agrawal
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Academy of Scientific and Innovative Research, New Delhi, India
| | - Amol Chhatrapati Bisen
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Academy of Scientific and Innovative Research, New Delhi, India
| | - Sachin Nashik Sanap
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Academy of Scientific and Innovative Research, New Delhi, India
| | - Sarvesh Kumar Verma
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Jawaharlal Nehru University, New Delhi, India
| | - Mukesh Kumar
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Jawaharlal Nehru University, New Delhi, India
| | - Anjali Mishra
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Academy of Scientific and Innovative Research, New Delhi, India
| | - Shivansh Kumar
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
| | - Mridula Chauhan
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
| | - Rabi Sankar Bhatta
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
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Sadikan MZ, Abdul Nasir NA. Diabetic retinopathy: emerging concepts of current and potential therapy. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2023; 396:3395-3406. [PMID: 37401966 DOI: 10.1007/s00210-023-02599-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Accepted: 06/22/2023] [Indexed: 07/05/2023]
Abstract
Diabetic retinopathy (DR) is one of the leading causes of permanent central blindness worldwide. Despite the complexity and inadequate understanding of DR pathogenesis, many of the underlying pathways are currently partially understood and may offer potential targets for future treatments. Anti-VEGF medications are currently the main medication for this problem. This article provides an overview of the established pharmacological treatments and those that are being developed to cure DR. We firstly reviewed the widely utilized approaches including pan-retinal photocoagulation therapy, anti-VEGF therapy, corticosteroid therapy, and surgical management of DR. Next, we discussed the mechanisms of action and prospective benefits of novel candidate medications. Current management are far from being a perfect treatment for DR, despite mild-term favorable efficiency and safety profiles. Pharmacological research should work toward developing longer-lasting treatments or new drug delivery systems, as well as on identifying new molecular targets in the pathogenetical mechanism for DR. In order to find a treatment that is specifically designed for each patient, it is also necessary to properly characterize patients, taking into account elements like hereditary factors and intraretinal neovascularization stages for effective utilization of drugs. The current and potential approaches for diabetic retinopathy. Image was constructed using Biorender.com.
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Affiliation(s)
- Muhammad Zulfiqah Sadikan
- Department of Pharmacology, Faculty of Medicine, Manipal University College Malaysia (MUCM), Bukit Baru, 75150, Malacca, Malaysia
| | - Nurul Alimah Abdul Nasir
- Department of Medical Education, Faculty of Medicine, Universiti Teknologi MARA, 47000, Sungai Buloh, Selangor, Malaysia.
- Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, 47000, Sungai Buloh, Selangor, Malaysia.
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Honisch C, Rodella U, Gatto C, Ruzza P, Tóthová JD. Oxidative Stress and Antioxidant-Based Interventional Medicine in Ophthalmology. Pharmaceuticals (Basel) 2023; 16:1146. [PMID: 37631061 PMCID: PMC10458870 DOI: 10.3390/ph16081146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 08/07/2023] [Accepted: 08/10/2023] [Indexed: 08/27/2023] Open
Abstract
The different anatomical compartments of the eye are highly subjected to reactive oxygen species (ROS) generation due to internal factors, such as metabolic high oxygen consumption, as well as environmental factors, including UV light. An antioxidant defense system is endowed in the eye tissues to regulate ROS quantity and activity. When this homeostatic system is overwhelmed, oxidative stress occurs, causing cellular damage, chronic inflammation, and tissue degeneration. It also plays a significant role in the development and progression of various ocular diseases. Understanding the mechanisms underlying oxidative stress in ocular conditions is thus crucial for the development of effective prevention and treatment strategies. To track marketed products based on antioxidant substances as active ingredients, the databases of the European Medicines Agency and the U.S. Food and Drug Administration were consulted. Only a limited number of items were identified, which were either used as therapeutic treatment or during ocular surgery, including antioxidants, synthetical derivatives, or pro-drugs designed to enhance tissue permeation and activity. This review aims to provide an overview of the primary ocular pathologies associated with oxidative stress and of the available pharmacological interventions centered around antioxidant molecules. Such insights are essential for advancing the development of effective prevention and novel treatment approaches.
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Affiliation(s)
- Claudia Honisch
- Institute of Biomolecular Chemistry of CNR (ICB-CNR), Via F. Marzolo, 1, 35131 Padova, Italy;
| | - Umberto Rodella
- Research and Development, AL.CHI.MI.A. S.R.L., Viale Austria, 14, 35020 Ponte San Nicolờ, Italy; (U.R.); (C.G.)
- Fondazione Banca degli Occhi del Veneto (FBOV), Via Paccagnella, 11, 30174 Zelarino, Italy
| | - Claudio Gatto
- Research and Development, AL.CHI.MI.A. S.R.L., Viale Austria, 14, 35020 Ponte San Nicolờ, Italy; (U.R.); (C.G.)
| | - Paolo Ruzza
- Institute of Biomolecular Chemistry of CNR (ICB-CNR), Via F. Marzolo, 1, 35131 Padova, Italy;
| | - Jana D’Amato Tóthová
- Research and Development, AL.CHI.MI.A. S.R.L., Viale Austria, 14, 35020 Ponte San Nicolờ, Italy; (U.R.); (C.G.)
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10
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Rusciano D, Bagnoli P. Pharmacotherapy and Nutritional Supplements for Neovascular Eye Diseases. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:1334. [PMID: 37512145 PMCID: PMC10383223 DOI: 10.3390/medicina59071334] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 06/27/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023]
Abstract
In this review, we aim to provide an overview of the recent findings about the treatment of neovascular retinal diseases. The use of conventional drugs and nutraceuticals endowed with antioxidant and anti-inflammatory properties that may support conventional therapies will be considered, with the final aim of achieving risk reduction (prevention) and outcome improvement (cooperation between treatments) of such sight-threatening proliferative retinopathies. For this purpose, we consider a medicinal product one that contains well-defined compound(s) with proven pharmacological and therapeutic effects, usually given for the treatment of full-blown diseases. Rarely are prescription drugs given for preventive purposes. A dietary supplement refers to a compound (often an extract or a mixture) used in the prevention or co-adjuvant treatment of a given pathology. However, it must be kept in mind that drug-supplement interactions may exist and might affect the efficacy of certain drug treatments. Moreover, the distinction between medicinal products and dietary supplements is not always straightforward. For instance, melatonin is formulated as a medicinal product for the treatment of sleep and behavioral problems; at low doses (usually below 1 mg), it is considered a nutraceutical, while at higher doses, it is sold as a psychotropic drug. Despite their lower status with respect to drugs, increasing evidence supports the notion of the beneficial effects of dietary supplements on proliferative retinopathies, a major cause of vision loss in the elderly. Therefore, we believe that, on a patient-by-patient basis, the administration of nutraceuticals, either alone or in association, could benefit many patients, delaying the progression of their disease and likely improving the efficacy of pharmaceutical drugs.
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Affiliation(s)
| | - Paola Bagnoli
- Department of Biology, University of Pisa, 56123 Pisa, Italy
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Bryl A, Mrugacz M, Falkowski M, Zorena K. A Mediterranean Diet May Be Protective in the Development of Diabetic Retinopathy. Int J Mol Sci 2023; 24:11145. [PMID: 37446322 DOI: 10.3390/ijms241311145] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 07/03/2023] [Accepted: 07/04/2023] [Indexed: 07/15/2023] Open
Abstract
The Mediterranean diet is recognized as one of the healthiest available dietary patterns. This perception results from its beneficial effects on the cardiovascular system and, also, on hypertension, diabetes, and cancer compared with other diets. Its impact on the course of diabetes is assessed in the available scientific literature; however, little information is available about its impact on diabetic retinopathy. The MD is characterized mainly by the consumption of fish, seafood, foods of plant origin, and fresh fruit and vegetables. It is also recommended to consume legumes, which are a source of folic acid, magnesium, iron, and dietary fiber. High consumption of nuts and unrefined grains is also recommended in the MD. Marine fish provide polyunsaturated acids from the omega-3 group. Olive oil plays a very important role, especially olive oil obtained from mechanical pressing. Additionally, olive oil contains vitamins E, K, and polyphenols. Polyphenols, which are present in a diverse range of vegetables, fruits, and seeds, have the ability to decrease oxidative stress, inflammation, and insulin resistance. Resveratrol is naturally found in grape skins and seeds, as well as in peanuts and berries, and is a constituent of red wine. Resveratrol can inhibit increased vascular leakage and loss of pericytes and regulate the level of VEGF protein in the retina, thus inhibiting the development of DR. Consumption of fruits, vegetables, fish, and olive oil may be correlated with a lower risk of diabetic retinopathy. This paper presents the definition of the Mediterranean diet and its influence on the course of diabetes and diabetic retinopathy.
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Affiliation(s)
- Anna Bryl
- Department of Ophthalmology and Eye Rehabilitation, Medical University of Bialystok, 15-089 Bialystok, Poland
| | - Małgorzata Mrugacz
- Department of Ophthalmology and Eye Rehabilitation, Medical University of Bialystok, 15-089 Bialystok, Poland
| | - Mariusz Falkowski
- PhD Studies, Medical University of Bialystok, 15-089 Bialystok, Poland
| | - Katarzyna Zorena
- Department of Immunobiology and Environmental Microbiology, Medical University of Gdansk, 80-211 Gdansk, Poland
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Li Y, Baccouche B, Del-Risco N, Park J, Song A, McAnany JJ, Kazlauskas A. The Slow Progression of Diabetic Retinopathy Is Associated with Transient Protection of Retinal Vessels from Death. Int J Mol Sci 2023; 24:10869. [PMID: 37446043 PMCID: PMC10341443 DOI: 10.3390/ijms241310869] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 06/22/2023] [Accepted: 06/23/2023] [Indexed: 07/15/2023] Open
Abstract
The purpose of this study was to investigate the reason that diabetic retinopathy (DR) is delayed from the onset of diabetes (DM) in diabetic mice. To this end, we tested the hypothesis that the deleterious effects of DM are initially tolerated because endogenous antioxidative defense is elevated and thereby confers resistance to oxidative stress-induced death. We found that this was indeed the case in both type 1 DM (T1D) and type 2 DM (T2D) mouse models. The retinal expression of antioxidant defense genes was increased soon after the onset of DM. In addition, ischemia/oxidative stress caused less death in the retinal vasculature of DM versus non-DM mice. Further investigation with T1D mice revealed that protection was transient; it waned as the duration of DM was prolonged. Finally, a loss of protection was associated with the manifestation of both neural and vascular abnormalities that are diagnostic of DR in mice. These observations demonstrate that DM can transiently activate protection from oxidative stress, which is a plausible explanation for the delay in the development of DR from the onset of DM.
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Affiliation(s)
- Yanliang Li
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA; (Y.L.); (B.B.); (N.D.-R.); (J.P.); (A.S.); (J.J.M.)
| | - Basma Baccouche
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA; (Y.L.); (B.B.); (N.D.-R.); (J.P.); (A.S.); (J.J.M.)
| | - Norma Del-Risco
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA; (Y.L.); (B.B.); (N.D.-R.); (J.P.); (A.S.); (J.J.M.)
| | - Jason Park
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA; (Y.L.); (B.B.); (N.D.-R.); (J.P.); (A.S.); (J.J.M.)
| | - Amy Song
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA; (Y.L.); (B.B.); (N.D.-R.); (J.P.); (A.S.); (J.J.M.)
| | - J. Jason McAnany
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA; (Y.L.); (B.B.); (N.D.-R.); (J.P.); (A.S.); (J.J.M.)
| | - Andrius Kazlauskas
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA; (Y.L.); (B.B.); (N.D.-R.); (J.P.); (A.S.); (J.J.M.)
- Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA
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Rondanelli M, Gasparri C, Riva A, Petrangolini G, Barrile GC, Cavioni A, Razza C, Tartara A, Perna S. Diet and ideal food pyramid to prevent or support the treatment of diabetic retinopathy, age-related macular degeneration, and cataracts. Front Med (Lausanne) 2023; 10:1168560. [PMID: 37324128 PMCID: PMC10265999 DOI: 10.3389/fmed.2023.1168560] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 05/09/2023] [Indexed: 06/17/2023] Open
Abstract
Many eye diseases, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and cataracts are preventable and treatable with lifestyle. The objective of this review is to assess the most recent research on the ideal dietary approach to prevent or support the treatment of DR, AMD, and cataracts, as well as to construct a food pyramid that makes it simple for people who are at risk of developing these pathologies to decide what to eat. The food pyramid presented here proposes what should be consumed every day: 3 portions of low glycemic index (GI) grains (for fiber and zinc content), 5 portions (each portion: ≥200 g/day) of fruits and vegetables (spinach, broccoli, zucchini cooked, green leafy vegetables, orange, kiwi, grapefruit for folic acid, vitamin C, and lutein/zeaxanthin content, at least ≥42 μg/day, are to be preferred), extra virgin olive (EVO) oil (almost 20 mg/day for vitamin E and polyphenols content), nuts or oil seeds (20-30 g/day, for zinc content, at least ≥15.8 mg/day); weekly: fish (4 portions, for omega-3 content and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) 0.35-1.4 g/day), white meat (3 portions for vitamin B12 content), legumes (2 portions for vegetal proteins), eggs (2 portions for lutein/zeaxanthin content), light cheeses (2 portions for vitamin B6 content), and almost 3-4 times/week microgreen and spices (saffron and curcumin). At the top of the pyramid, there are two pennants: one green, which indicates the need for personalized supplementation (if daily requirements cannot be met through diet, omega-3, and L-methylfolate supplementation), and one red, which indicates that certain foods are prohibited (salt and sugar). Finally, 3-4 times per week, 30-40 min of aerobic and resistance exercises are required.
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Affiliation(s)
- Mariangela Rondanelli
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Mondino Foundation, Pavia, Italy
- Unit of Human and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy
| | - Clara Gasparri
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia, Italy
| | | | | | - Gaetan Claude Barrile
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia, Italy
| | - Alessandro Cavioni
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia, Italy
| | - Claudia Razza
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia, Italy
| | - Alice Tartara
- Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona “Istituto Santa Margherita”, University of Pavia, Pavia, Italy
| | - Simone Perna
- Department of Biology, College of Science, University of Bahrain, Zallaq, Bahrain
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Perais J, Agarwal R, Evans JR, Loveman E, Colquitt JL, Owens D, Hogg RE, Lawrenson JG, Takwoingi Y, Lois N. Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy. Cochrane Database Syst Rev 2023; 2:CD013775. [PMID: 36815723 PMCID: PMC9943918 DOI: 10.1002/14651858.cd013775.pub2] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
BACKGROUND Diabetic retinopathy (DR) is characterised by neurovascular degeneration as a result of chronic hyperglycaemia. Proliferative diabetic retinopathy (PDR) is the most serious complication of DR and can lead to total (central and peripheral) visual loss. PDR is characterised by the presence of abnormal new blood vessels, so-called "new vessels," at the optic disc (NVD) or elsewhere in the retina (NVE). PDR can progress to high-risk characteristics (HRC) PDR (HRC-PDR), which is defined by the presence of NVD more than one-fourth to one-third disc area in size plus vitreous haemorrhage or pre-retinal haemorrhage, or vitreous haemorrhage or pre-retinal haemorrhage obscuring more than one disc area. In severe cases, fibrovascular membranes grow over the retinal surface and tractional retinal detachment with sight loss can occur, despite treatment. Although most, if not all, individuals with diabetes will develop DR if they live long enough, only some progress to the sight-threatening PDR stage. OBJECTIVES: To determine risk factors for the development of PDR and HRC-PDR in people with diabetes and DR. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 5), Ovid MEDLINE, and Ovid Embase. The date of the search was 27 May 2022. Additionally, the search was supplemented by screening reference lists of eligible articles. There were no restrictions to language or year of publication. SELECTION CRITERIA: We included prospective or retrospective cohort studies and case-control longitudinal studies evaluating prognostic factors for the development and progression of PDR, in people who have not had previous treatment for DR. The target population consisted of adults (≥18 years of age) of any gender, sexual orientation, ethnicity, socioeconomic status, and geographical location, with non-proliferative diabetic retinopathy (NPDR) or PDR with less than HRC-PDR, diagnosed as per standard clinical practice. Two review authors independently screened titles and abstracts, and full-text articles, to determine eligibility; discrepancies were resolved through discussion. We considered prognostic factors measured at baseline and any other time points during the study and in any clinical setting. Outcomes were evaluated at three and eight years (± two years) or lifelong. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from included studies using a data extraction form that we developed and piloted prior to the data collection stage. We resolved any discrepancies through discussion. We used the Quality in Prognosis Studies (QUIPS) tool to assess risk of bias. We conducted meta-analyses in clinically relevant groups using a random-effects approach. We reported hazard ratios (HR), odds ratios (OR), and risk ratios (RR) separately for each available prognostic factor and outcome, stratified by different time points. Where possible, we meta-analysed adjusted prognostic factors. We evaluated the certainty of the evidence with an adapted version of the GRADE framework. MAIN RESULTS: We screened 6391 records. From these, we identified 59 studies (87 articles) as eligible for inclusion. Thirty-five were prospective cohort studies, 22 were retrospective studies, 18 of which were cohort and six were based on data from electronic registers, and two were retrospective case-control studies. Twenty-three studies evaluated participants with type 1 diabetes (T1D), 19 with type 2 diabetes (T2D), and 17 included mixed populations (T1D and T2D). Studies on T1D included between 39 and 3250 participants at baseline, followed up for one to 45 years. Studies on T2D included between 100 and 71,817 participants at baseline, followed up for one to 20 years. The studies on mixed populations of T1D and T2D ranged from 76 to 32,553 participants at baseline, followed up for four to 25 years. We found evidence indicating that higher glycated haemoglobin (haemoglobin A1c (HbA1c)) levels (adjusted OR ranged from 1.11 (95% confidence interval (CI) 0.93 to 1.32) to 2.10 (95% CI 1.64 to 2.69) and more advanced stages of retinopathy (adjusted OR ranged from 1.38 (95% CI 1.29 to 1.48) to 12.40 (95% CI 5.31 to 28.98) are independent risk factors for the development of PDR in people with T1D and T2D. We rated the evidence for these factors as of moderate certainty because of moderate to high risk of bias in the studies. There was also some evidence suggesting several markers for renal disease (for example, nephropathy (adjusted OR ranged from 1.58 (95% CI not reported) to 2.68 (2.09 to 3.42), and creatinine (adjusted meta-analysis HR 1.61 (95% CI 0.77 to 3.36)), and, in people with T1D, age at diagnosis of diabetes (< 12 years of age) (standardised regression estimate 1.62, 95% CI 1.06 to 2.48), increased triglyceride levels (adjusted RR 1.55, 95% CI 1.06 to 1.95), and larger retinal venular diameters (RR 4.28, 95% CI 1.50 to 12.19) may increase the risk of progression to PDR. The certainty of evidence for these factors, however, was low to very low, due to risk of bias in the included studies, inconsistency (lack of studies preventing the grading of consistency or variable outcomes), and imprecision (wide CIs). There was no substantial and consistent evidence to support duration of diabetes, systolic or diastolic blood pressure, total cholesterol, low- (LDL) and high- (HDL) density lipoproteins, gender, ethnicity, body mass index (BMI), socioeconomic status, or tobacco and alcohol consumption as being associated with incidence of PDR. There was insufficient evidence to evaluate prognostic factors associated with progression of PDR to HRC-PDR. AUTHORS' CONCLUSIONS: Increased HbA1c is likely to be associated with progression to PDR; therefore, maintaining adequate glucose control throughout life, irrespective of stage of DR severity, may help to prevent progression to PDR and risk of its sight-threatening complications. Renal impairment in people with T1D or T2D, as well as younger age at diagnosis of diabetes mellitus (DM), increased triglyceride levels, and increased retinal venular diameters in people with T1D may also be associated with increased risk of progression to PDR. Given that more advanced DR severity is associated with higher risk of progression to PDR, the earlier the disease is identified, and the above systemic risk factors are controlled, the greater the chance of reducing the risk of PDR and saving sight.
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Affiliation(s)
- Jennifer Perais
- The Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK
| | - Ridhi Agarwal
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Jennifer R Evans
- Cochrane Eyes and Vision, Queen's University Belfast, Belfast, UK
| | | | | | | | - Ruth E Hogg
- Centre for Public Health, Queen's University Belfast, Belfast, UK
| | - John G Lawrenson
- Centre for Applied Vision Research, School of Health Sciences, City University of London, London, UK
| | - Yemisi Takwoingi
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Noemi Lois
- Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK
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15
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Xie E, Nadeem U, Xie B, D’Souza M, Sulakhe D, Skondra D. Using Computational Drug-Gene Analysis to Identify Novel Therapeutic Candidates for Retinal Neuroprotection. Int J Mol Sci 2022; 23:ijms232012648. [PMID: 36293505 PMCID: PMC9604082 DOI: 10.3390/ijms232012648] [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: 08/03/2022] [Revised: 10/11/2022] [Accepted: 10/18/2022] [Indexed: 01/24/2023] Open
Abstract
Retinal cell death is responsible for irreversible vision loss in many retinal disorders. No commercially approved treatments are currently available to attenuate retinal cell loss and preserve vision. We seek to identify chemicals/drugs with thoroughly-studied biological functions that possess neuroprotective effects in the retina using a computational bioinformatics approach. We queried the National Center for Biotechnology Information (NCBI) to identify genes associated with retinal neuroprotection. Enrichment analysis was performed using ToppGene to identify compounds related to the identified genes. This analysis constructs a Pharmacome from multiple drug-gene interaction databases to predict compounds with statistically significant associations to genes involved in retinal neuroprotection. Compounds with known deleterious effects (e.g., asbestos, ethanol) or with no clinical indications (e.g., paraquat, ozone) were manually filtered. We identified numerous drug/chemical classes associated to multiple genes implicated in retinal neuroprotection using a systematic computational approach. Anti-diabetics, lipid-lowering medicines, and antioxidants are among the treatments anticipated by this analysis, and many of these drugs could be readily repurposed for retinal neuroprotection. Our technique serves as an unbiased tool that can be utilized in the future to lead focused preclinical and clinical investigations for complex processes such as neuroprotection, as well as a wide range of other ocular pathologies.
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Affiliation(s)
- Edward Xie
- Chicago Medical School at Rosalind, Franklin University of Medicine and Science, Chicago, IL 60064, USA
| | - Urooba Nadeem
- Department of Pathology, University of Chicago, Chicago, IL 60637, USA
| | - Bingqing Xie
- Department of Medicine, University of Chicago, Chicago, IL 60637, USA
| | - Mark D’Souza
- Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA
| | - Dinanath Sulakhe
- Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA
| | - Dimitra Skondra
- Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA
- Correspondence:
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16
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Combined drug triads for synergic neuroprotection in retinal degeneration. Biomed Pharmacother 2022; 149:112911. [DOI: 10.1016/j.biopha.2022.112911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 03/28/2022] [Accepted: 03/29/2022] [Indexed: 11/23/2022] Open
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17
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Carpi-Santos R, de Melo Reis RA, Gomes FCA, Calaza KC. Contribution of Müller Cells in the Diabetic Retinopathy Development: Focus on Oxidative Stress and Inflammation. Antioxidants (Basel) 2022; 11:617. [PMID: 35453302 PMCID: PMC9027671 DOI: 10.3390/antiox11040617] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/01/2022] [Accepted: 03/15/2022] [Indexed: 01/27/2023] Open
Abstract
Diabetic retinopathy is a neurovascular complication of diabetes and the main cause of vision loss in adults. Glial cells have a key role in maintenance of central nervous system homeostasis. In the retina, the predominant element is the Müller cell, a specialized cell with radial morphology that spans all retinal layers and influences the function of the entire retinal circuitry. Müller cells provide metabolic support, regulation of extracellular composition, synaptic activity control, structural organization of the blood-retina barrier, antioxidant activity, and trophic support, among other roles. Therefore, impairments of Müller actions lead to retinal malfunctions. Accordingly, increasing evidence indicates that Müller cells are affected in diabetic retinopathy and may contribute to the severity of the disease. Here, we will survey recently described alterations in Müller cell functions and cellular events that contribute to diabetic retinopathy, especially related to oxidative stress and inflammation. This review sheds light on Müller cells as potential therapeutic targets of this disease.
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Affiliation(s)
- Raul Carpi-Santos
- Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil; (R.C.-S.); (F.C.A.G.)
| | - Ricardo A. de Melo Reis
- Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil;
| | - Flávia Carvalho Alcantara Gomes
- Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil; (R.C.-S.); (F.C.A.G.)
| | - Karin C. Calaza
- Instituto de Biologia, Departamento de Neurobiologia, Universidade Federal Fluminense, Niteroi 24210-201, RJ, Brazil
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18
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The Effect of Diet and Lifestyle on the Course of Diabetic Retinopathy-A Review of the Literature. Nutrients 2022; 14:nu14061252. [PMID: 35334909 PMCID: PMC8955064 DOI: 10.3390/nu14061252] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 03/10/2022] [Accepted: 03/14/2022] [Indexed: 12/23/2022] Open
Abstract
Diabetes is a major social problem. As shown by epidemiological studies, the world incidence of diabetes is increasing and so is the number of people suffering from its complications. Therefore, it is important to determine possible preventive tools. In the prevention of diabetic retinopathy, it is essential to control glycemia, lipid profile and blood pressure. This can be done not only by pharmacological treatment, but first of all by promoting a healthy lifestyle, changing dietary habits and increasing physical activity. In our work, we present a review of the literature to show that physical exercise and an adequate diet can significantly reduce the risk of diabetes and diabetic retinopathy.
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19
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Understanding Neurodegeneration from a Clinical and Therapeutic Perspective in Early Diabetic Retinopathy. Nutrients 2022; 14:nu14040792. [PMID: 35215442 PMCID: PMC8877033 DOI: 10.3390/nu14040792] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 02/10/2022] [Accepted: 02/11/2022] [Indexed: 02/05/2023] Open
Abstract
Recent evidence indicates that neurodegeneration is a critical element of diabetic retinopathy (DR) pathogenesis. The neuronal cells’ apoptosis contributes to microvascular impairment and blood–retinal barrier breakdown. Therefore, neurodegeneration represents an early intervention target to slow and prevent the development of microvascular alterations visible on clinical examination. Multimodal imaging features and functional assessment can permit the identification of neuronal damage in a subclinical stage before the recognition of DR signs. Clinical features of neurodegeneration are crucial in identifying patients at high risk of developing a vascular impairment and, thus, serve as outcome measures to understand the efficacy of supplementation. The optimal approach for targeting neurodegeneration contemplates the use of topical compounds that possibly act on different elements of the pathogenic cascade. To date, clinical trials available on humans tested three different topical agents, including brimonidine, somatostatin, and citicoline, with promising results.
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20
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Canovai A, Amato R, Melecchi A, Dal Monte M, Rusciano D, Bagnoli P, Cammalleri M. Preventive Efficacy of an Antioxidant Compound on Blood Retinal Barrier Breakdown and Visual Dysfunction in Streptozotocin-Induced Diabetic Rats. Front Pharmacol 2022; 12:811818. [PMID: 35046830 PMCID: PMC8762314 DOI: 10.3389/fphar.2021.811818] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 12/06/2021] [Indexed: 12/13/2022] Open
Abstract
In diabetic retinopathy (DR), high blood glucose drives chronic oxidative stress and inflammation that trigger alterations of the neurovascular balance finally resulting in vascular abnormalities and retinal cell death, which converge towards altered electroretinogram (ERG). In the last years, a growing body of preclinical evidence has suggested that nutrients with anti-inflammatory/antioxidant properties can be able to hamper DR progression since its very early stages. In the present study, we used a streptozotocin-induced rat model of DR, which mimics most aspects of the early stages of human DR, to test the preventive efficacy of a novel compound containing cyanidin-3-glucoside (C3G), verbascoside and zinc as nutrients with antioxidant and anti-inflammatory properties. Western blot, immunofluorescence and electroretinographic analyses demonstrated a dose-dependent inhibition of oxidative stress- and inflammation-related mechanisms, with a significant counterpart in preventing molecular mechanisms leading to DR-associated vasculopathy and its related retinal damage. Preventive efficacy of the compound on dysfunctional a- and b-waves was also demonstrated by electroretinography. The present demonstration that natural compounds, possibly as a consequence of vascular rescue following ameliorated oxidative stress and inflammation, may prevent the apoptotic cascade leading to ERG dysfunction, adds further relevance to the potential application of antioxidants as a preventive therapy to counteract DR progression.
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Affiliation(s)
| | - Rosario Amato
- Department of Biology, University of Pisa, Pisa, Italy
| | | | - Massimo Dal Monte
- Department of Biology, University of Pisa, Pisa, Italy.,Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy
| | | | - Paola Bagnoli
- Department of Biology, University of Pisa, Pisa, Italy
| | - Maurizio Cammalleri
- Department of Biology, University of Pisa, Pisa, Italy.,Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy
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21
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Piñas García P, Hernández Martínez FJ, Aznárez López N, Castillón Torre L, Tena Sempere ME. Supplementation with a Highly Concentrated Docosahexaenoic Acid (DHA) in Non-Proliferative Diabetic Retinopathy: A 2-Year Randomized Double-Blind Placebo-Controlled Study. Antioxidants (Basel) 2022; 11:antiox11010116. [PMID: 35052620 PMCID: PMC8772895 DOI: 10.3390/antiox11010116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 12/28/2021] [Accepted: 01/03/2022] [Indexed: 02/04/2023] Open
Abstract
We assessed the effect of a 2-year supplementation with a highly concentrated docosahexaenoic acid (DHA) product with antioxidant activity on non-proliferative diabetic retinopathy (NPDR) in a randomized double-blind placebo-controlled study. A total of 170 patients with diabetes were randomly assigned to the DHA group (n = 83) or the placebo group (n = 87). NPDR was diagnosed using non-contact slit lamp biomicroscopy examination, and classified into mild, moderate, and severe stages. Patients in the DHA group received a high rich DHA triglyceride (1050 mg/day) nutritional supplement, and those in the placebo group received olive oil capsules. The percentages of mild NPDR increased from 61.7% at baseline to 75.7% at the end of the study in the DHA group, and from 61.9% to 73.1% in the placebo group. Moderate NPDR stages decreased from 35.1% at baseline to 18.7% at the end of the study in the DHA group, and from 36.8% to 26.0% in the placebo group. In the DHA group, there were five eyes with severe NPDR at baseline, which increased to one more at the end of the study. In the placebo group, of two eyes with severe NPDR at baseline, one eye remained at the end of the study. Changes in visual acuity were not found. There were improvements in the serum levels of HbA1c in both groups, but significant differences between the DHA and the placebo groups were not found. In this study, the use of a DHA triglyceride nutraceutical supplement for 2 years did not appear to influence the slowing of the progression of NPDR.
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Szymanska M, Mahmood D, Yap TE, Cordeiro MF. Recent Advancements in the Medical Treatment of Diabetic Retinal Disease. Int J Mol Sci 2021; 22:ijms22179441. [PMID: 34502350 PMCID: PMC8430918 DOI: 10.3390/ijms22179441] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 08/24/2021] [Accepted: 08/25/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetic retinal disease remains one of the most common complications of diabetes mellitus (DM) and a leading cause of preventable blindness. The mainstay of management involves glycemic control, intravitreal, and laser therapy. However, intravitreal therapy commonly requires frequent hospital visits and some patients fail to achieve a significant improvement in vision. Novel and long-acting therapies targeting a range of pathways are warranted, while evidence to support optimal combinations of treatments is currently insufficient. Improved understanding of the molecular pathways involved in pathogenesis is driving the development of therapeutic agents not only targeting visible microvascular disease and metabolic derangements, but also inflammation and accelerated retinal neurodegeneration. This review summarizes the current and emerging treatments of diabetic retinal diseases and provides an insight into the future of managing this important condition.
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Affiliation(s)
- Maja Szymanska
- The Imperial College Ophthalmic Research Group (ICORG), Imperial College London, London NW1 5QH, UK; (M.S.); (D.M.); (T.E.Y.)
| | - Daanyaal Mahmood
- The Imperial College Ophthalmic Research Group (ICORG), Imperial College London, London NW1 5QH, UK; (M.S.); (D.M.); (T.E.Y.)
| | - Timothy E. Yap
- The Imperial College Ophthalmic Research Group (ICORG), Imperial College London, London NW1 5QH, UK; (M.S.); (D.M.); (T.E.Y.)
| | - Maria F. Cordeiro
- The Imperial College Ophthalmic Research Group (ICORG), Imperial College London, London NW1 5QH, UK; (M.S.); (D.M.); (T.E.Y.)
- The Western Eye Hospital, Imperial College Healthcare NHS Trust (ICHNT), London NW1 5QH, UK
- Glaucoma and Retinal Neurodegeneration Group, Department of Visual Neuroscience, UCL Institute of Ophthalmology, London EC1V 9EL, UK
- Correspondence:
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Dammak A, Huete-Toral F, Carpena-Torres C, Martin-Gil A, Pastrana C, Carracedo G. From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment. Pharmaceutics 2021; 13:1376. [PMID: 34575451 PMCID: PMC8467715 DOI: 10.3390/pharmaceutics13091376] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/16/2021] [Accepted: 08/20/2021] [Indexed: 12/17/2022] Open
Abstract
Most irreversible blindness observed with glaucoma and retina-related ocular diseases, including age-related macular degeneration and diabetic retinopathy, have their origin in the posterior segment of the eye, making their physiopathology both complex and interconnected. In addition to the age factor, these diseases share the same mechanism disorder based essentially on oxidative stress. In this context, the imbalance between the production of reactive oxygen species (ROS) mainly by mitochondria and their elimination by protective mechanisms leads to chronic inflammation. Oxidative stress and inflammation share a close pathophysiological process, appearing simultaneously and suggesting a relationship between both mechanisms. The biochemical end point of these two biological alarming systems is the release of different biomarkers that can be used in the diagnosis. Furthermore, oxidative stress, initiating in the vulnerable tissue of the posterior segment, is closely related to mitochondrial dysfunction, apoptosis, autophagy dysfunction, and inflammation, which are involved in each disease progression. In this review, we have analyzed (1) the oxidative stress and inflammatory processes in the back of the eye, (2) the importance of biomarkers, detected in systemic or ocular fluids, for the diagnosis of eye diseases based on recent studies, and (3) the treatment of posterior ocular diseases, based on long-term clinical studies.
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Affiliation(s)
- Azza Dammak
- Ocupharm Group Research, Faculty of Optic and Optometry, University Complutense of Madrid, C/Arcos del Jalon 118, 28037 Madrid, Spain; (A.D.); (F.H.-T.); (C.C.-T.); (A.M.-G.); (C.P.)
| | - Fernando Huete-Toral
- Ocupharm Group Research, Faculty of Optic and Optometry, University Complutense of Madrid, C/Arcos del Jalon 118, 28037 Madrid, Spain; (A.D.); (F.H.-T.); (C.C.-T.); (A.M.-G.); (C.P.)
| | - Carlos Carpena-Torres
- Ocupharm Group Research, Faculty of Optic and Optometry, University Complutense of Madrid, C/Arcos del Jalon 118, 28037 Madrid, Spain; (A.D.); (F.H.-T.); (C.C.-T.); (A.M.-G.); (C.P.)
| | - Alba Martin-Gil
- Ocupharm Group Research, Faculty of Optic and Optometry, University Complutense of Madrid, C/Arcos del Jalon 118, 28037 Madrid, Spain; (A.D.); (F.H.-T.); (C.C.-T.); (A.M.-G.); (C.P.)
| | - Cristina Pastrana
- Ocupharm Group Research, Faculty of Optic and Optometry, University Complutense of Madrid, C/Arcos del Jalon 118, 28037 Madrid, Spain; (A.D.); (F.H.-T.); (C.C.-T.); (A.M.-G.); (C.P.)
| | - Gonzalo Carracedo
- Ocupharm Group Research, Faculty of Optic and Optometry, University Complutense of Madrid, C/Arcos del Jalon 118, 28037 Madrid, Spain; (A.D.); (F.H.-T.); (C.C.-T.); (A.M.-G.); (C.P.)
- Department of Optometry and Vsiion, Faculty of Optic and Optometry, University Complutense of Madrid, C/Arcos del Jalon 118, 28037 Madrid, Spain
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Valero-Vello M, Peris-Martínez C, García-Medina JJ, Sanz-González SM, Ramírez AI, Fernández-Albarral JA, Galarreta-Mira D, Zanón-Moreno V, Casaroli-Marano RP, Pinazo-Duran MD. Searching for the Antioxidant, Anti-Inflammatory, and Neuroprotective Potential of Natural Food and Nutritional Supplements for Ocular Health in the Mediterranean Population. Foods 2021; 10:1231. [PMID: 34071459 PMCID: PMC8229954 DOI: 10.3390/foods10061231] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 05/24/2021] [Accepted: 05/25/2021] [Indexed: 12/14/2022] Open
Abstract
Adherence to a healthy diet offers a valuable intervention to compete against the increasing cases of ocular diseases worldwide, such as dry eye disorders, myopia progression, cataracts, glaucoma, diabetic retinopathy, or age macular degeneration. Certain amounts of micronutrients must be daily provided for proper functioning of the visual system, such as vitamins, carotenoids, trace metals and omega-3 fatty acids. Among natural foods, the following have to be considered for boosting eye/vision health: fish, meat, eggs, nuts, legumes, citrus fruits, nuts, leafy green vegetables, orange-colored fruits/vegetables, olives-olive oil, and dairy products. Nutritional supplements have received much attention as potential tools for managing chronic-degenerative ocular diseases. A systematic search of PubMed, Web of Science, hand-searched publications and historical archives were performed by the professionals involved in this study, to include peer-reviewed articles in which natural food, nutrient content, and its potential relationship with ocular health. Five ophthalmologists and two researchers collected the characteristics, quality and suitability of the above studies. Finally, 177 publications from 1983 to 2021 were enclosed, mainly related to natural food, Mediterranean diet (MedDiet) and nutraceutic supplementation. For the first time, original studies with broccoli and tigernut (chufa de Valencia) regarding the ocular surface dysfunction, macular degeneration, diabetic retinopathy and glaucoma were enclosed. These can add value to the diet, counteract nutritional defects, and help in the early stages, as well as in the course of ophthalmic pathologies. The main purpose of this review, enclosed in the Special Issue "Health Benefits and Nutritional Quality of Fruits, Nuts and Vegetables," is to identify directions for further research on the role of diet and nutrition in the eyes and vision, and the potential antioxidant, anti-inflammatory and neuroprotective effects of natural food (broccoli, saffron, tigernuts and walnuts), the Mediterranean Diet, and nutraceutic supplements that may supply a promising and highly affordable scenario for patients at risk of vision loss. This review work was designed and carried out by a multidisciplinary group involved in ophthalmology and ophthalmic research and especially in nutritional ophthalmology.
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Affiliation(s)
- Mar Valero-Vello
- Ophthalmic Research Unit “Santiago Grisolía” Foundation for the Promotion of Health and Biomedical Research of Valencia FISABIO, 46017 Valencia, Spain; (M.V.-V.); (J.J.G.-M.); (S.M.S.-G.); (M.D.P.-D.)
| | - Cristina Peris-Martínez
- Ophthalmic Medical Center (FOM), Foundation for the Promotion of Health and Biomedical Research of Valencia (FISABIO), 46015 Valencia, Spain;
- Department of Surgery, University of Valencia, 46019 Valencia, Spain
- Spanish Net of Ophthalmic Research “OFTARED” RD16/0008/0022, Institute of Health Carlos III, 28029 Madrid, Spain; (A.I.R.); (D.G.-M.); (R.P.C.-M.)
| | - José J. García-Medina
- Ophthalmic Research Unit “Santiago Grisolía” Foundation for the Promotion of Health and Biomedical Research of Valencia FISABIO, 46017 Valencia, Spain; (M.V.-V.); (J.J.G.-M.); (S.M.S.-G.); (M.D.P.-D.)
- Spanish Net of Ophthalmic Research “OFTARED” RD16/0008/0022, Institute of Health Carlos III, 28029 Madrid, Spain; (A.I.R.); (D.G.-M.); (R.P.C.-M.)
- Department of Ophthalmology, General University Hospital “Morales Meseguer”, 30007 Murcia, Spain
- Department of Ophthalmology and Optometry, University of Murcia, 30120 Murcia, Spain
| | - Silvia M. Sanz-González
- Ophthalmic Research Unit “Santiago Grisolía” Foundation for the Promotion of Health and Biomedical Research of Valencia FISABIO, 46017 Valencia, Spain; (M.V.-V.); (J.J.G.-M.); (S.M.S.-G.); (M.D.P.-D.)
- Spanish Net of Ophthalmic Research “OFTARED” RD16/0008/0022, Institute of Health Carlos III, 28029 Madrid, Spain; (A.I.R.); (D.G.-M.); (R.P.C.-M.)
- Cellular and Molecular Ophthalmobiology Group, Department of Surgery, Faculty of Medicine and Odontology, University of Valencia, 46010 Valencia, Spain
| | - Ana I. Ramírez
- Spanish Net of Ophthalmic Research “OFTARED” RD16/0008/0022, Institute of Health Carlos III, 28029 Madrid, Spain; (A.I.R.); (D.G.-M.); (R.P.C.-M.)
- Department of Immunology, Ophthalmology and Otorrinolaringology, Institute of Ophthalmic Research “Ramón Castroviejo”, Complutense University of Madrid, 28040 Madrid, Spain;
| | - José A. Fernández-Albarral
- Department of Immunology, Ophthalmology and Otorrinolaringology, Institute of Ophthalmic Research “Ramón Castroviejo”, Complutense University of Madrid, 28040 Madrid, Spain;
| | - David Galarreta-Mira
- Spanish Net of Ophthalmic Research “OFTARED” RD16/0008/0022, Institute of Health Carlos III, 28029 Madrid, Spain; (A.I.R.); (D.G.-M.); (R.P.C.-M.)
- Department of Ophthalmology. University Clinic Hospital of Valladolid, 47003 Valladolid, Spain
| | - Vicente Zanón-Moreno
- Ophthalmic Research Unit “Santiago Grisolía” Foundation for the Promotion of Health and Biomedical Research of Valencia FISABIO, 46017 Valencia, Spain; (M.V.-V.); (J.J.G.-M.); (S.M.S.-G.); (M.D.P.-D.)
- Spanish Net of Ophthalmic Research “OFTARED” RD16/0008/0022, Institute of Health Carlos III, 28029 Madrid, Spain; (A.I.R.); (D.G.-M.); (R.P.C.-M.)
- Faculty of Health Sciences, International University of Valencia, 46002 Valencia, Spain
| | - Ricardo P. Casaroli-Marano
- Spanish Net of Ophthalmic Research “OFTARED” RD16/0008/0022, Institute of Health Carlos III, 28029 Madrid, Spain; (A.I.R.); (D.G.-M.); (R.P.C.-M.)
- Departament of Surgery, School of Medicine and Health Sciences, Clinic Hospital of Barcelona, Universitat de Barcelona, 08036 Barcelona, Spain
| | - María D. Pinazo-Duran
- Ophthalmic Research Unit “Santiago Grisolía” Foundation for the Promotion of Health and Biomedical Research of Valencia FISABIO, 46017 Valencia, Spain; (M.V.-V.); (J.J.G.-M.); (S.M.S.-G.); (M.D.P.-D.)
- Spanish Net of Ophthalmic Research “OFTARED” RD16/0008/0022, Institute of Health Carlos III, 28029 Madrid, Spain; (A.I.R.); (D.G.-M.); (R.P.C.-M.)
- Cellular and Molecular Ophthalmobiology Group, Department of Surgery, Faculty of Medicine and Odontology, University of Valencia, 46010 Valencia, Spain
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Role of Oral Antioxidant Supplementation in the Current Management of Diabetic Retinopathy. Int J Mol Sci 2021; 22:ijms22084020. [PMID: 33924714 PMCID: PMC8069935 DOI: 10.3390/ijms22084020] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 04/07/2021] [Accepted: 04/09/2021] [Indexed: 12/13/2022] Open
Abstract
Oxidative stress has been postulated as an underlying pathophysiologic mechanism of diabetic retinopathy (DR), the main cause of avoidable blindness in working-aged people. This review addressed the current daily clinical practice of DR and the role of antioxidants in this practice. A systematic review of the studies on antioxidant supplementation in DR patients was presented. Fifteen studies accomplished the inclusion criteria. The analysis of these studies concluded that antioxidant supplementation has a IIB level of recommendation in adult Type 1 and Type 2 diabetes mellitus subjects without retinopathy or mild-to-moderate nonproliferative DR without diabetic macular oedema as a complementary therapy together with standard medical care.
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Plasma fatty acids and primary open-angle glaucoma in the elderly: the Montrachet population-based study. BMC Ophthalmol 2021; 21:146. [PMID: 33757477 PMCID: PMC7986303 DOI: 10.1186/s12886-021-01910-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 03/11/2021] [Indexed: 11/10/2022] Open
Abstract
Background To compare plasma fatty acids (FAs) between participants with primary open-angle glaucoma (POAG) and participants without neuropathy in an elderly population and to investigate specific FAs pattern in POAG. Methods We conducted a population-based study in participants older than 75 years. Participants underwent a comprehensive eye examination with optic nerve photographs, visual field test and optic nerve OCT with RNFL thickness measurement. Glaucomatous status was defined according to the International Society for Epidemiologic and Geographical Ophthalmology classification. Lipids were extracted from plasma and FAs methylesters prepared and analyzed by gas chromatography-mass spectrometry. Results Among the 1153 participants of the Montrachet study 810 were retained for analysis and 68 had POAG. The mean age was 82.11 ± 3.67. In multivariable analysis FAs levels were not different between POAG participants and controls (P = 0.078). A FAs pattern characterized by high negative weight of gamma-linoleic acid, eicosapentaenoic acid polyunsaturated FAs (PUFAs), Cis-7 hexadecenoic acid monounsaturated FAs (MUFAs) and high positive weight of eicosadienoic acid, docosatetraenoic acid, docosapentaenoic n-6, alpha linoleic acid PUFAs, eicosenoic acid MUFAs, margaric acid and behenic acid saturated FAs was positively associated with POAG. After adjustment for major confounders, individuals in the upper tertile of FAs pattern scores compared with those in the lower tertile were more likely to present POAG (OR = 3.09 [95% CI 1.29–7.40] P = 0.013). Conclusions We found no significant difference regarding isolated plasma FAs between participants with POAG and participants without neuropathy in elderly but specific FAs pattern might be associated with POAG.
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Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease. Antioxidants (Basel) 2020; 9:antiox9100905. [PMID: 32977483 PMCID: PMC7598160 DOI: 10.3390/antiox9100905] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 09/17/2020] [Accepted: 09/18/2020] [Indexed: 12/11/2022] Open
Abstract
Diabetic retinopathy (DR), a common chronic complication of diabetes mellitus and the leading cause of vision loss in the working-age population, is clinically defined as a microvascular disease that involves damage of the retinal capillaries with secondary visual impairment. While its clinical diagnosis is based on vascular pathology, DR is associated with early abnormalities in the electroretinogram, indicating alterations of the neural retina and impaired visual signaling. The pathogenesis of DR is complex and likely involves the simultaneous dysregulation of multiple metabolic and signaling pathways through the retinal neurovascular unit. There is evidence that microvascular disease in DR is caused in part by altered energetic metabolism in the neural retina and specifically from signals originating in the photoreceptors. In this review, we discuss the main pathogenic mechanisms that link alterations in neural retina bioenergetics with vascular regression in DR. We focus specifically on the recent developments related to alterations in mitochondrial metabolism including energetic substrate selection, mitochondrial function, oxidation-reduction (redox) imbalance, and oxidative stress, and critically discuss the mechanisms of these changes and their consequences on retinal function. We also acknowledge implications for emerging therapeutic approaches and future research directions to find novel mitochondria-targeted therapeutic strategies to correct bioenergetics in diabetes. We conclude that retinal bioenergetics is affected in the early stages of diabetes with consequences beyond changes in ATP content, and that maintaining mitochondrial integrity may alleviate retinal disease.
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Update on the Effects of Antioxidants on Diabetic Retinopathy: In Vitro Experiments, Animal Studies and Clinical Trials. Antioxidants (Basel) 2020; 9:antiox9060561. [PMID: 32604941 PMCID: PMC7346101 DOI: 10.3390/antiox9060561] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 06/22/2020] [Accepted: 06/23/2020] [Indexed: 12/14/2022] Open
Abstract
Current therapies for diabetic retinopathy (DR) incorporate blood glucose and blood pressure control, vitrectomy, photocoagulation, and intravitreal injections of anti-vascular endothelial growth factors or corticosteroids. Nonetheless, these techniques have not been demonstrated to completely stop the evolution of this disorder. The pathophysiology of DR is not fully known, but there is more and more evidence indicating that oxidative stress is an important mechanism in the progression of DR. In this sense, antioxidants have been suggested as a possible therapy to reduce the complications of DR. In this review we aim to assemble updated information in relation to in vitro experiments, animal studies and clinical trials dealing with the effect of the antioxidants on DR.
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Shi C, Wang P, Airen S, Brown C, Liu Z, Townsend JH, Wang J, Jiang H. Nutritional and medical food therapies for diabetic retinopathy. EYE AND VISION (LONDON, ENGLAND) 2020; 7:33. [PMID: 32582807 PMCID: PMC7310218 DOI: 10.1186/s40662-020-00199-y] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 05/28/2020] [Indexed: 02/07/2023]
Abstract
Diabetic retinopathy (DR) is a form of microangiopathy. Reducing oxidative stress in the mitochondria and cell membranes decreases ischemic injury and end-organ damage to the retina. New approaches are needed, which reduce the risk and improve the outcomes of DR while complementing current therapeutic approaches. Homocysteine (Hcy) elevation and oxidative stress are potential therapeutic targets in DR. Common genetic polymorphisms such as those of methylenetetrahydrofolate reductase (MTHFR), increase Hcy and DR risk and severity. Patients with DR have high incidences of deficiencies of crucial vitamins, minerals, and related compounds, which also lead to elevation of Hcy and oxidative stress. Addressing the effects of the MTHFR polymorphism and addressing comorbid deficiencies and insufficiencies reduce the impact and severity of the disease. This approach provides safe and simple strategies that support conventional care and improve outcomes. Suboptimal vitamin co-factor availability also impairs the release of neurotrophic and neuroprotective growth factors. Collectively, this accounts for variability in presentation and response of DR to conventional therapy. Fortunately, there are straightforward recommendations for addressing these issues and supporting traditional treatment plans. We have reviewed the literature for nutritional interventions that support conventional therapies to reduce disease risk and severity. Optimal combinations of vitamins B1, B2, B6, L-methylfolate, methylcobalamin (B12), C, D, natural vitamin E complex, lutein, zeaxanthin, alpha-lipoic acid, and n-acetylcysteine are identified for protecting the retina and choroid. Certain medical foods have been successfully used as therapy for retinopathy. Recommendations based on this review and our clinical experience are developed for clinicians to use to support conventional therapy for DR. DR from both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have similar retinal findings and responses to nutritional therapies.
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Affiliation(s)
- Ce Shi
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 1638 NW 10th Avenue, McKnight Building - Room 202A, Miami, FL 33136 USA
- School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Peng Wang
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 1638 NW 10th Avenue, McKnight Building - Room 202A, Miami, FL 33136 USA
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Shriya Airen
- College of Arts and Sciences, University of Miami, Miami, FL USA
| | - Craig Brown
- Department of Ophthalmology, College of Medicine, the University of Arkansas for Medical Sciences, Fayetteville, AR USA
| | - Zhiping Liu
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 1638 NW 10th Avenue, McKnight Building - Room 202A, Miami, FL 33136 USA
- Ophthalmic Center, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong China
| | - Justin H. Townsend
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 1638 NW 10th Avenue, McKnight Building - Room 202A, Miami, FL 33136 USA
| | - Jianhua Wang
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 1638 NW 10th Avenue, McKnight Building - Room 202A, Miami, FL 33136 USA
| | - Hong Jiang
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 1638 NW 10th Avenue, McKnight Building - Room 202A, Miami, FL 33136 USA
- Department of Neurology, University of Miami Miller School of Medicine, Miami, FL USA
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Sanz-González SM, Raga-Cervera J, Aguirre Lipperheide M, Zanón-Moreno V, Chiner V, Ramírez AI, Pinazo-Durán MD. Effect of an oral supplementation with a formula containing R-lipoic acid in glaucoma patients. ACTA ACUST UNITED AC 2020; 95:120-129. [PMID: 31980324 DOI: 10.1016/j.oftal.2019.11.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 11/11/2019] [Accepted: 11/19/2019] [Indexed: 12/27/2022]
Abstract
OBJECTIVE To analyse the safety and effectiveness of the oral administration of a commercialised supplement containing R-alpha lipoic acid, taurine, vitamins C and E, lutein, zeaxanthin, zinc, copper and docosahexaenoic acid, in patients with primary open angle glaucoma (POAG), and in control subjects. MATERIAL AND METHODS A prospective study of cases and controls was carried out, including 30 participants of both genders that were divided into: POAG Group (n=15) and a control group (CG; n=15), assigned to the oral intake of NuaDHA preparations Vision® (1 pill/day)+NuaDHA 1000 (2 pills/day) for 6 months. Participants were interviewed, ophthalmologically examined, and peripheral blood was taken for routine analysis and the determination of the pro-oxidant (malondialdehyde) and total antioxidant status. Statistical analysis was performed using the SPSS 22.0 program. RESULTS After 6 months of supplementation, there was a significant increase in the plasma total antioxidant status (1.073±0.090mM vs 1.276±0.107mM, P=.028), along with a parallel decrease in malondialdehyde (7.066±1.070μM vs 2.771±0.462μM, P=.005) in the POAG group. The malondialdehyde also decreased in the control group (6.17±1.336 vs. 2.51±0.391, P=.028). The Schirmer test improved (20-30%) and the subjective dry eye signs/symptoms noticeably decreased in the POAG group versus the CG. CONCLUSIONS Formulations containing antioxidant vitamins, R-alpha lipoic acid and docosahexaenoic acid, administered for 6 consecutive months, counteracted the oxidative stress by further stabilising the morphological/functional parameters of both the ocular surface and the glaucoma, without presenting with adverse effects or intolerances.
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Affiliation(s)
- S M Sanz-González
- Unidad de Investigación Oftalmológica Santiago Grisolía/FISABIO y Grupo de Investigación de la Universidad de Valencia en Oftalmo-biología Celular y Molecular, Valencia, España; Red de Oftalmología de la RETICS: RD16-0008: «Prevención, detección precoz, tratamiento y rehabilitación de las patologías oculares», Instituto de Salud Carlos III, Madrid, España
| | - J Raga-Cervera
- Unidad de Investigación Oftalmológica Santiago Grisolía/FISABIO y Grupo de Investigación de la Universidad de Valencia en Oftalmo-biología Celular y Molecular, Valencia, España; Departamento de Oftalmología,Hospital de Manises, Manises, Valencia, España
| | | | - V Zanón-Moreno
- Unidad de Investigación Oftalmológica Santiago Grisolía/FISABIO y Grupo de Investigación de la Universidad de Valencia en Oftalmo-biología Celular y Molecular, Valencia, España; Red de Oftalmología de la RETICS: RD16-0008: «Prevención, detección precoz, tratamiento y rehabilitación de las patologías oculares», Instituto de Salud Carlos III, Madrid, España; Universidad Internacional de Valencia, Área de Salud, Valencia, España; Departamento de Medicina Preventiva y Salud Pública, Facultad de Medicina y Odontología. Universidad de Valencia, Valencia, España
| | - V Chiner
- Departamento de Oftalmología, Hospital Universitario Dr. Peset. Valencia, España
| | - A I Ramírez
- Red de Oftalmología de la RETICS: RD16-0008: «Prevención, detección precoz, tratamiento y rehabilitación de las patologías oculares», Instituto de Salud Carlos III, Madrid, España; Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Madrid, España.
| | - M D Pinazo-Durán
- Unidad de Investigación Oftalmológica Santiago Grisolía/FISABIO y Grupo de Investigación de la Universidad de Valencia en Oftalmo-biología Celular y Molecular, Valencia, España; Red de Oftalmología de la RETICS: RD16-0008: «Prevención, detección precoz, tratamiento y rehabilitación de las patologías oculares», Instituto de Salud Carlos III, Madrid, España; Departamento de Cirugía, Facultad de Medicina y Odontología, Universidad de Valencia, Valencia, España.
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Tabatabaei-Malazy O, Ardeshirlarijani E, Namazi N, Nikfar S, Jalili RB, Larijani B. Dietary antioxidative supplements and diabetic retinopathy; a systematic review. J Diabetes Metab Disord 2019; 18:705-716. [PMID: 31890694 PMCID: PMC6915253 DOI: 10.1007/s40200-019-00434-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 08/20/2019] [Indexed: 12/11/2022]
Abstract
PURPOSE There is controversial data regarding the effects of dietary antioxidative supplements on diabetic retinopathy (DR). We conducted a systematic review of both observational and randomized controlled clinical trials (RCTs) to clarify whether they are effective or not. METHODS All observational and RCTs conducted by antioxidative supplements on DR published up to 1 January 2018 in PubMed, Web of Sciences, Scopus and Cochrane Library databases were included. Exclusion criteria were animal studies, and studies conducted in Type 1 diabetes mellitus (T1DM), children or pregnant women. Main outcome measures were reporting the incidence or progression of DR in T2DM by assessment of visual fields, and measurements of oxidative and antioxidative biomarkers. The quality of reporting of included articles and risk of bias were assessed. RESULTS Finally, we reached 14 observational studies and 7 RCTs that conducted on 256,259 subjects. Due to severe methodological heterogeneity, only qualitative synthesis was carried. All studies were reported a significantly lower level of antioxidants and higher level of oxidative stress biomarkers in DR compared with others. There was an inverse significant correlation between vitamin C and malondialdehyde (MDA) (r = -0.81) or DNA damage (r = -0.41). These figures were statistically significant between vitamin E and MDA (r = 0.77) or superoxide dismutase (r = 0.44). Coefficient of correlation between MDA and zinc (-0.82), coenzyme Q10 (0.56), and magnesium (-0.73) was significant. Multi-oxidants trials were shown non-significant beneficial effects on DR. CONCLUSIONS Although our study supports the positive effects of antioxidative supplements on DR, more high quality studies are needed to confirm.
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Affiliation(s)
- Ozra Tabatabaei-Malazy
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Nazli Namazi
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Shekoufeh Nikfar
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Personalized Medicine Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Evidence-based Evaluation of Cost-Effectiveness and Clinical Outcomes Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
- Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy and Pharmaceutical Policy Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Baradar Jalili
- Department of Surgery, University of British Columbia, Vancouver, British Columbia Canada
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Gurreri A, Pazzaglia A, Schiavi C. Role of Statins and Ascorbic Acid in the Natural History of Diabetic Retinopathy: A New, Affordable Therapy? Ophthalmic Surg Lasers Imaging Retina 2019; 50:S23-S27. [DOI: 10.3928/23258160-20190108-06] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 03/21/2019] [Indexed: 12/30/2022]
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Hegazy AM, El-Sayed EM, Ibrahim KS, Abdel-Azeem AS. Dietary antioxidant for disease prevention corroborated by the Nrf2 pathway. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2019; 16:/j/jcim.ahead-of-print/jcim-2018-0161/jcim-2018-0161.xml. [PMID: 30726190 DOI: 10.1515/jcim-2018-0161] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Accepted: 10/28/2018] [Indexed: 12/11/2022]
Abstract
Dietary antioxidants are widely distributed in various types of our food. They are strongly associated with reduced risk of many chronic diseases such as atherosclerosis, cancer, and Alzheimer's diseases. They include vitamins such as vitamins A, E, C, and carotenoids. Also, some minerals like; zinc, manganese, copper, iron, and selenium are essential for the activity of antioxidant enzymes. Furthermore, dietary polyphenols and flavonoids are considered as potent antioxidant compounds. Vegetables, fruits, and edible herbs are the richest sources of such antioxidants. Antioxidants reduce oxidative stress, either directly by reducing reactive species or indirectly by enhancing the body antioxidant defense mechanisms in different ways. These may include upregulating gene expression of some antioxidant enzymes via a nuclear factor erythroid 2 related factor2 pathway. Administration of a mixture of antioxidants is beneficial since they act synergistically in various phases. The aims of this review are to summarize the different antioxidants from dietary sources and their role in the prevention of different diseases.
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Affiliation(s)
- Amany M Hegazy
- Department of Nutrition and Food Sciences, National Research Centre, Dokki, Giza, Egypt
| | - Eman M El-Sayed
- Department of Nutrition and Food Sciences, National Research Centre, Dokki, Giza, Egypt
| | - Khadiga S Ibrahim
- Department of Environmental and Occupational Medicine, National Research Centre, Dokki, Giza, Egypt
| | - Amal S Abdel-Azeem
- Department of Nutrition and Food Sciences, National Research Centre, Dokki, Giza, Egypt
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Homme RP, Singh M, Majumder A, George AK, Nair K, Sandhu HS, Tyagi N, Lominadze D, Tyagi SC. Remodeling of Retinal Architecture in Diabetic Retinopathy: Disruption of Ocular Physiology and Visual Functions by Inflammatory Gene Products and Pyroptosis. Front Physiol 2018; 9:1268. [PMID: 30233418 PMCID: PMC6134046 DOI: 10.3389/fphys.2018.01268] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Accepted: 08/21/2018] [Indexed: 02/06/2023] Open
Abstract
Diabetic patients suffer from a host of physiological abnormalities beyond just those of glucose metabolism. These abnormalities often lead to systemic inflammation via modulation of several inflammation-related genes, their respective gene products, homocysteine metabolism, and pyroptosis. The very nature of this homeostatic disruption re-sets the overall physiology of diabetics via upregulation of immune responses, enhanced retinal neovascularization, upregulation of epigenetic events, and disturbances in cells' redox regulatory system. This altered pathophysiological milieu can lead to the development of diabetic retinopathy (DR), a debilitating vision-threatening eye condition with microvascular complications. DR is the most prevalent cause of irreversible blindness in the working-age adults throughout the world as it can lead to severe structural and functional remodeling of the retina, decreasing vision and thus diminishing the quality of life. In this manuscript, we attempt to summarize recent developments and new insights to explore the very nature of this intertwined crosstalk between components of the immune system and their metabolic orchestrations to elucidate the pathophysiology of DR. Understanding the multifaceted nature of the cellular and molecular factors that are involved in DR could reveal new targets for effective diagnostics, therapeutics, prognostics, preventive tools, and finally strategies to combat the development and progression of DR in susceptible subjects.
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Affiliation(s)
- Rubens P. Homme
- Eye and Vision Science Laboratory, Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States
- Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States
| | - Mahavir Singh
- Eye and Vision Science Laboratory, Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States
- Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States
| | - Avisek Majumder
- Eye and Vision Science Laboratory, Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States
- Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, United States
| | - Akash K. George
- Eye and Vision Science Laboratory, Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States
- Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States
| | - Kavya Nair
- Eye and Vision Science Laboratory, Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States
- Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States
| | - Harpal S. Sandhu
- Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY, United States
- Kentucky Lions Eye Center, University of Louisville School of Medicine, Louisville, KY, United States
| | - Neetu Tyagi
- Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States
| | - David Lominadze
- Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States
| | - Suresh C Tyagi
- Department of Physiology, University of Louisville School of Medicine, Louisville, KY, United States
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Serum Extracellular Superoxide Dismutase Is Associated with Diabetic Retinopathy Stage in Chinese Patients with Type 2 Diabetes Mellitus. DISEASE MARKERS 2018; 2018:8721379. [PMID: 29849828 PMCID: PMC5937587 DOI: 10.1155/2018/8721379] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2017] [Revised: 12/26/2017] [Accepted: 02/20/2018] [Indexed: 02/08/2023]
Abstract
Extracellular superoxide dismutase (ecSOD) is the major extracellular scavenger of reactive oxygen species and associated with the diabetic complication in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the serum ecSOD activity in Chinese patients with different stages of diabetic retinopathy (DR) and evaluate the association between the serum ecSOD activity and the severity of DR. A total of 343 T2DM patients were categorized into three groups: nondiabetic retinopathy (NDR) group, nonproliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. Serum ecSOD activities were measured by the autoxidation of the pyrogallol method. In this study, 271, 46, and 26 patients were enrolled in the NDR, NPDR, and PDR groups, respectively. We found a significantly decreased trend of serum ecSOD activity among NDR subjects (118.0 ± 11.5 U/mL) compared to NPDR subjects (108.5 ± 11.9 U/mL) (P < 0.001) and NPDR subjects compared to PDR subjects (102.7 ± 12.4 U/mL) (P = 0.041). Serum ecSOD activity was an independent risk factor for DR (OR = 0.920, P < 0.001) and was associated with the progression of DR. Serum ecSOD activity might be a biomarker for DR screening and evaluation of the clinical severity of DR in Chinese T2DM patients.
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Manukumar HM, Shiva Kumar J, Chandrasekhar B, Raghava S, Umesha S. Evidences for diabetes and insulin mimetic activity of medicinal plants: Present status and future prospects. Crit Rev Food Sci Nutr 2018; 57:2712-2729. [PMID: 26857927 DOI: 10.1080/10408398.2016.1143446] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Diabetes mellitus (DM) is a considerable systemic metabolic disorder to exhibit various metabolic and cardiovascular disorders, mainly hyperglycemia. The global projected estimate of diabetes in 2030 will be about 439 million adults, out of which 300 million expected are of type-2 diabetes mellitus (T2DM). The present knowledge revealed responsible factors, occurrence and mechanism of these factors involved in the DM diseases. Hence, the aim of this review is to address and summarize the causes, plant resources, importance, present status and future programmes for diabetes control. The present review answers the contemporary present questions raised in the scientific field on DM. Two major problems are explained in detail about the autoimmune attack or dysfunction of β-cell and insulin resistance involved for Type 1 and Type 2 DM, respectively. Though there are various approaches to reduce the ill effects of diabetes and its secondary complications, many preferred herbal formulations due to lesser side effects and low cost. For this reason still it is getting increased attention in searching antidiabetic medicinal plants for hot research and to develop targeted medicine. Recurrence of islet autoimmunity lesson from pancreatic islet cell transplantation to cure T1D was outlined. With these highlights, the review summarizes the current knowledge on diabetes occurrence, factors (environmental and genetics), and types (I, II, gestation, and secondary DM), antidiabetic plants, sources for insulin mimetic plant principle compounds and their target mechanism with current and future trusted research areas for controlling of DM.
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Affiliation(s)
- H M Manukumar
- a Department of Studies in Biotechnology , University of Mysore , Manasagangotri, Mysore , Karnataka , India
| | - J Shiva Kumar
- a Department of Studies in Biotechnology , University of Mysore , Manasagangotri, Mysore , Karnataka , India
| | - B Chandrasekhar
- a Department of Studies in Biotechnology , University of Mysore , Manasagangotri, Mysore , Karnataka , India
| | - Sri Raghava
- a Department of Studies in Biotechnology , University of Mysore , Manasagangotri, Mysore , Karnataka , India
| | - S Umesha
- a Department of Studies in Biotechnology , University of Mysore , Manasagangotri, Mysore , Karnataka , India
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Ischemic Retinopathies: Oxidative Stress and Inflammation. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2017; 2017:3940241. [PMID: 29410732 PMCID: PMC5749295 DOI: 10.1155/2017/3940241] [Citation(s) in RCA: 111] [Impact Index Per Article: 13.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/17/2017] [Accepted: 11/20/2017] [Indexed: 12/15/2022]
Abstract
Ischemic retinopathies (IRs), such as retinopathy of prematurity (ROP), diabetic retinopathy (DR), and (in many cases) age-related macular degeneration (AMD), are ocular disorders characterized by an initial phase of microvascular changes that results in ischemia, followed by a second phase of abnormal neovascularization that may culminate into retinal detachment and blindness. IRs are complex retinal conditions in which several factors play a key role during the development of the different pathological stages of the disease. Increasing evidence reveals that oxidative stress and inflammatory processes are important contributors to the pathogenesis of IRs. Despite the beneficial effects of the photocoagulation and anti-VEGF therapy during neovascularization phase, the need to identify novel targets to prevent initial phases of these ocular pathologies is still needed. In this review, we provide an update on the involvement of oxidative stress and inflammation in the progression of IRs and address some therapeutic interventions by using antioxidants and anti-inflammatory agents.
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Diet and risk of diabetic retinopathy: a systematic review. Eur J Epidemiol 2017; 33:141-156. [DOI: 10.1007/s10654-017-0338-8] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2017] [Accepted: 11/27/2017] [Indexed: 12/11/2022]
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Abstract
Current evidence suggests lutein and its isomers play important roles in ocular development in utero and throughout the life span, in vision performance in young and later adulthood, and in lowering risk for the development of common age-related eye diseases in older age. These xanthophyll (oxygen-containing) carotenoids are found in a wide variety of vegetables and fruits, and they are present in especially high concentrations in leafy green vegetables. Additionally, egg yolks and human milk appear to be bioavailable sources. The prevalence of lutein, zeaxanthin, and meso-zeaxanthin in supplements is increasing. Setting optimal and safe ranges of intake requires additional research, particularly in pregnant and lactating women. Accumulating evidence about variable interindividual response to dietary intake of these carotenoids, based on genetic or metabolic influences, suggests that there may be subgroups that benefit from higher levels of intake and/or alternate strategies to improve lutein and zeaxanthin status.
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Affiliation(s)
- Julie Mares
- Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin 53726-2336;
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Sahli MW, Mares JA, Meyers KJ, Klein R, Brady WE, Klein BEK, Ochs-Balcom HM, Donahue RP, Millen AE. Dietary Intake of Lutein and Diabetic Retinopathy in the Atherosclerosis Risk in Communities Study (ARIC). Ophthalmic Epidemiol 2016; 23:99-108. [PMID: 26949989 PMCID: PMC4861223 DOI: 10.3109/09286586.2015.1129426] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
PURPOSE We tested the hypothesis that dietary intake of lutein is inversely associated with prevalence of diabetic retinopathy (DR) due to its antioxidant and anti-inflammatory properties and location within the retina. METHODS We used logistic regression to examine the association between prevalent DR and energy-adjusted lutein intake by quartile (Q) using data collected from 1430 Atherosclerosis Risk in Communities Study (ARIC) participants with diabetes (n = 994 white, n = 508 black). DR was assessed from 45° non-mydriatic retinal photographs of one randomly chosen eye taken at visit 3 (1993-1995). Dietary lutein intake was estimated using a 66-item food frequency questionnaire at visit 1 (1987-1989). RESULTS Median estimated daily lutein intake was 1370 µg/1000 kcals and prevalence of DR was ~21%. We found a crude association between lutein and DR (odds ratio, OR, 2.11, 95% confidence interval, CI, 1.45-3.09 for Q4, high intake, vs. Q1, low intake; p for trend <0.0001), which was attenuated after adjustment for ethnicity, duration of diabetes, glycosylated hemoglobin levels, field center and energy intake (OR 1.41, 95% CI 0.87-2.28; p for trend = 0.01). In analyses limited to persons with short diabetes duration (<6 years), the association no longer persisted (OR 0.94, 95% CI 0.31-2.16; p for trend =0.72) compared to the association in those with longer diabetes duration (≥6 years; OR 1.58, 95% CI 0.91-2.75; p for trend = 0.01). CONCLUSION Contrary to our hypothesis, we found that the odds of higher lutein intake were greater among those with DR than those without DR. However, after adjusting for confounders, intake of lutein was not associated with DR.
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Affiliation(s)
- Michelle W. Sahli
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, NY
| | - Julie A. Mares
- Department of Ophthalmology and Visual Sciences, The University of Wisconsin-Madison, Madison, WI
| | - Kristin J. Meyers
- Department of Ophthalmology and Visual Sciences, The University of Wisconsin-Madison, Madison, WI
| | - Ronald Klein
- Department of Ophthalmology and Visual Sciences, The University of Wisconsin-Madison, Madison, WI
| | - William E. Brady
- Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY
| | - Barbara E. K. Klein
- Department of Ophthalmology and Visual Sciences, The University of Wisconsin-Madison, Madison, WI
| | - Heather M. Ochs-Balcom
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, NY
| | - Richard P. Donahue
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, NY
| | - Amy E. Millen
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, 270 Farber Hall, Buffalo, NY 14214-8001. Telephone: (716) 829-5377, Fax: (716) 829-2979
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Enhanced Oxidative Stress and Other Potential Biomarkers for Retinopathy in Type 2 Diabetics: Beneficial Effects of the Nutraceutic Supplements. BIOMED RESEARCH INTERNATIONAL 2015; 2015:408180. [PMID: 26618168 PMCID: PMC4649073 DOI: 10.1155/2015/408180] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Revised: 08/28/2015] [Accepted: 08/31/2015] [Indexed: 12/28/2022]
Abstract
We have studied the global risk of retinopathy in a Mediterranean population of type 2 diabetes mellitus (T2DM) patients, according to clinical, biochemical, and lifestyle biomarkers. The effects of the oral supplementation containing antioxidants/omega 3 fatty acids (A/ω3) were also evaluated. Suitable participants were distributed into two main groups: (1) T2DMG (with retinopathy (+DR) or without retinopathy (-DR)) and (2) controls (CG). Participants were randomly assigned (+A/ω3) or not (-A/ω3) to the oral supplementation with a daily pill of Nutrof Omega (R) for 18 months. Data collected including demographics, anthropometrics, characteristics/lifestyle, ophthalmic examination (best corrected visual acuity, ocular fundus photographs, and retinal thickness as assessed by optical coherence tomography), and blood parameters (glucose, glycosylated hemoglobin, triglycerides, malondialdehyde, and total antioxidant capacity) were registered, integrated, and statistically processed by the SPSS 15.0 program. Finally, 208 participants (130 diabetics (68 +DR/62 -DR) and 78 controls) completed the follow-up. Blood analyses confirmed that the T2DMG+DR patients had significantly higher oxidative stress (p < 0.05), inflammatory (p < 0.05), and vascular (p < 0.001) risk markers than the T2DMG-DR and the CG. Furthermore, the A/ω3 oral supplementation positively changed the baseline parameters, presumptively by inducing metabolic activation and ameliorating the ocular health after 18 months of supplementation.
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Pinazo-Durán MD, Zanón-Moreno V, Gallego-Pinazo R, García-Medina JJ. Oxidative stress and mitochondrial failure in the pathogenesis of glaucoma neurodegeneration. PROGRESS IN BRAIN RESEARCH 2015; 220:127-53. [PMID: 26497788 DOI: 10.1016/bs.pbr.2015.06.001] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
This review focuses on oxidative stress and mitochondrial failure for understanding mechanisms of optic nerve damage in primary open-angle glaucoma. The chapter shows scientific evidence for the role of mitochondrial disbalance and reactive oxygen species in glaucoma neurodegeneration. Mitochondria regulate important cellular functions including reactive oxygen species generation and apoptosis. Mitochondrial alterations result from a wide variety of damaging sources. Reactive oxygen species formed by the mitochondria can act as signaling molecules, inducing lipid peroxidation and/or excitotoxicity with the result of cell lesion and death. Antioxidants may help to counteract oxidative stress and to promote neuroprotection. We provide information that may lead to a new way for diagnosing and treating glaucoma patients.
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Affiliation(s)
- Maria D Pinazo-Durán
- Ophthalmic Research Unit "Santiago Grisolía", University Hospital Dr. Peset, Valencia, Spain; Department of Surgery/Ophthalmology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain.
| | - Vicente Zanón-Moreno
- Ophthalmic Research Unit "Santiago Grisolía", University Hospital Dr. Peset, Valencia, Spain; Department of Surgery/Ophthalmology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
| | - Roberto Gallego-Pinazo
- Ophthalmic Research Unit "Santiago Grisolía", University Hospital Dr. Peset, Valencia, Spain; Department of Ophthalmology, University and Polytechnic Hospital la Fe, Valencia, Spain
| | - José J García-Medina
- Ophthalmic Research Unit "Santiago Grisolía", University Hospital Dr. Peset, Valencia, Spain; Department of Ophthalmology, University Hospital Reina Sofia, Murcia, Spain; Department of Ophthalmology and Optometry, University of Murcia, Murcia, Spain
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Garcia-Medina JJ, Garcia-Medina M, Garrido-Fernandez P, Galvan-Espinosa J, Garcia-Maturana C, Zanon-Moreno V, Pinazo-Duran MD. A two-year follow-up of oral antioxidant supplementation in primary open-angle glaucoma: an open-label, randomized, controlled trial. Acta Ophthalmol 2015; 93:546-54. [PMID: 25545196 DOI: 10.1111/aos.12629] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Accepted: 11/11/2014] [Indexed: 02/04/2023]
Abstract
PURPOSE To evaluate the effect of oral antioxidant supplementation (OAS) on primary open-angle glaucoma (POAG) over a 2-year follow-up period. PATIENTS AND METHODS In this open-label, randomized controlled trial, 117 eyes of 117 patients with mild or moderate POAG and intraocular pressure under control with topical antiglaucoma medications were recruited and randomly divided into three groups according to supplementation: (1) OAS with (ICAPS R(®) - Alcon Laboratories, n = 26); (2) OAS without ω-3 fatty acids (OFTAN MACULA(®) - Laboratorios Esteve, n = 28); and (3) a control group without OAS (n = 63). They all underwent visual field (VF) tests (Humphrey 24-2) and scans using a Fourier-domain optical coherence tomography (FD-OCT) device (RTVue-100) at the beginning of the study and 2 years later. Mean deviation (MD), standard pattern deviation (PSD), peripapillary retinal nerve fibre layer (RNFL) and macular ganglion cell complex (GCC) parameters were considered for the analysis. Patients were also classified according to MD deterioration (fast deterioration vs. slow deterioration). RESULTS Visual field global indices, peripapillary RNFL thickness and macular GCC thickness showed no differences among the groups at the beginning and end of the follow-up. Besides all the comparisons among groups for differences before and after the follow-up of the MD, PSD, RNFL and GCC parameters were also non-significant. The proportions of patients according to MD deterioration were similar among the groups and subgroups (p > 0.05 for all the comparisons). CONCLUSION Oral antioxidant supplementation with or without ω-3 fatty acids does not appear useful as an adjuvant treatment of mild/moderate POAG in the short term.
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Affiliation(s)
- Jose Javier Garcia-Medina
- Department of Ophthalmology; Huercal Overa Hospital; Almeria Spain
- Department of Ophthalmology; Reina Sofia University Hospital; Murcia Spain
- Department of Ophthalmology and Optometry; School of Medicine; University of Murcia; Murcia Spain
- Ophthalmology Research Unit “Santiago Grisolia”; Valencia Spain
| | - Manuel Garcia-Medina
- Department of Ophthalmology; Torrecardenas Hospital; Almeria Spain
- Head of the Andalusian Ophthalmic Research Group (GIAO); Almería Spain
| | - Pablo Garrido-Fernandez
- Eastern Andalusian Biosanitary Research Foundation “Alejandro Otero” (FIBAO); Torrecardenas Hospital; Almeria Spain
| | - Jose Galvan-Espinosa
- Eastern Andalusian Biosanitary Research Foundation “Alejandro Otero” (FIBAO); Torrecardenas Hospital; Almeria Spain
| | | | - Vicente Zanon-Moreno
- Genetic and Molecular Epidemiology Unit; Department of Preventive Medicine & Public Health; School of Medicine; University of Valencia; Valencia Spain
| | - Maria Dolores Pinazo-Duran
- Ophthalmology Research Unit “Santiago Grisolia”; Valencia Spain
- Department of Ophthalmology; School of Medicine; University of Valencia; Valencia Spain
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Pourahmadi Z, Mahboob S, Saedisomeolia A, Reykandeh MT. The Effect of Tomato Juice Consumption on Antioxidant Status in Overweight and Obese Females. Women Health 2015; 55:795-804. [PMID: 26086066 DOI: 10.1080/03630242.2015.1050546] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Tomatoes and their products are the main source of lycopene, a powerful potent antioxidant. Tomato products improve antioxidant defenses and reduce the risk of oxidative stress, at least partly, due to the presence of lycopene. Lycopene, as an antioxidant, induces the upregulation of antioxidant enzymes and reinforces the total enzyme capacity of the human body. Obesity is a chronic condition in which destructive mechanisms increase the reactive oxygen species and attenuation of antioxidant status. We hypothesized that the consumption of a lycopene-rich food would improve the antioxidant defense of women who were overweight or obese. A total of seventy-five overweight or obese female students of the Tehran University of Medical Sciences were enrolled and randomly allocated to one of two groups, intervention (n = 40) or control (n = 35), consuming 330 ml/d of tomato juice or water, respectively, for a 20-day period. At baseline and day 20, total antioxidant capacity and antioxidant enzyme activity (superoxide dismutase, glutathione peroxidase, and catalase) were analyzed using ELISA kits and spectrophotometric methods and then compared between the two groups. Lycopene consumption had no effect on these aforementioned variables. Therefore, it seems that more research with longer duration and more sensitive indicators will be required.
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Affiliation(s)
- Zohre Pourahmadi
- a Faculty of Nutrition , Tabriz University of Medical Science , Tabriz , Iran
| | - Soltanali Mahboob
- b Nutrition Research Center, Faculty of Nutrition , Tabriz University of Medical Science , Tabriz , Iran
| | - Ahmad Saedisomeolia
- c Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics , Tehran University of Medical Sciences , Tehran , Iran
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Ola MS, Alhomida AS. Neurodegeneration in diabetic retina and its potential drug targets. Curr Neuropharmacol 2014; 12:380-386. [PMID: 25342945 PMCID: PMC4207077 DOI: 10.2174/1570159x12666140619205024] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Revised: 04/27/2014] [Accepted: 06/19/2014] [Indexed: 12/04/2022] Open
Abstract
Diabetic retinopathy (DR) is one of the major complications of diabetes causing vision loss and blindness worldwide. DR is widely recognized as a neurodegenerative disease as evidenced from early changes at cellular and molecular levels in the neuronal component of the diabetic retina, which is further supported by various retinal functional tests indicating functional deficits in the retina soon after diabetes progression. Diabetes alters the level of a number of neurodegenerative metabolites, which increases influx through several metabolic pathways which in turn induce an increase in oxidative stress and a decrease in neurotrophic factors, thereby damage retinal neurons. Loss of neurons may implicate in vascular pathology, a clinical signs of DR observed at later stages of the disease. Here, we discuss diabetes-induced potential metabolites known to be detrimental to neuronal damage and their mechanism of action. In addition, we highlight important neurotrophic factors, whose level have been found to be dysregulated in diabetic retina and may damage neurons. Furthermore, we discuss potential drugs and strategies based on targeting diabetes-induced metabolites, metabolic pathways, oxidative stress, and neurotrophins to protect retinal neurons, which may ameliorate vision loss and vascular damage in DR.
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Affiliation(s)
- Mohammad Shamsul Ola
- Department of Biochemistry, College of Science, King Saud University, Riyadh, KSA, Saudi Arabia
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El-Abhar HS, Schaalan MF. Phytotherapy in diabetes: Review on potential mechanistic perspectives. World J Diabetes 2014; 5:176-197. [PMID: 24748931 PMCID: PMC3990312 DOI: 10.4239/wjd.v5.i2.176] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2013] [Revised: 01/07/2014] [Accepted: 03/14/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus (DM) is a widely spread epidemic disease that results from the absence of insulin, decreased secretion and/or impaired function. Since DM is a multi-factorial disease, the available pharmaceuticals, despite their sensible treatment, target mostly one pathway to control hyperglycemia and encounter several side effects. Therefore, new therapeutic paradigms aim to hit several pathways using only one agent. Traditionally, antidiabetic plants and/or their active constituents may fulfill this need. More than 200 species of plants possess antidiabetic properties which were evaluated mostly by screening tests without digging far for the exact mode of action. Searching among the different literature resources and various database and in view of the above aspects, the present article provides a comprehensive review on the available antidiabetic plants that have been approved by pharmacological and clinical evaluations, and which their mechanism(s) of action is assured. These plants are categorized according to their proved mode of action and are classified into those that act by inhibiting glucose absorption from intestine, increasing insulin secretion from the pancreas, inhibiting glucose production from hepatocytes, or enhancing glucose uptake by adipose and muscle tissues. The current review also highlights those that mimic in their action the new peptide analogs, such as exenatide, liraglutide and dipeptidylpeptidase-4 inhibitors that increase glucagon-like peptide-1 serum concentration and slow down the gastric emptying.
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Pinazo-Durán MD, Gallego-Pinazo R, García-Medina JJ, Zanón-Moreno V, Nucci C, Dolz-Marco R, Martínez-Castillo S, Galbis-Estrada C, Marco-Ramírez C, López-Gálvez MI, Galarreta DJ, Díaz-Llópis M. Oxidative stress and its downstream signaling in aging eyes. Clin Interv Aging 2014; 9:637-52. [PMID: 24748782 PMCID: PMC3990383 DOI: 10.2147/cia.s52662] [Citation(s) in RCA: 86] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Oxidative stress (OS) and its biomarkers are the biochemical end point of the imbalance between reactive oxygen species (ROS) production and the ability of the antioxidant (AOX) biological systems to fight against oxidative injury. OBJECTIVE We reviewed the role of OS and its downstream signaling in aging eyes. METHODS A search of the literature and current knowledge on the physiological and pathological mechanisms of OS were revisited in relation to the eyes and the aging process. Most prevalent ocular diseases have been analyzed herein in relation to OS and nutraceutic supplements, such as dry-eye disorders, glaucoma, age-related macular degeneration, and diabetic retinopathy. RESULTS Clinical, biochemical, and molecular data from anterior and posterior eye segment diseases point to OS as the common pathogenic mechanism in the majority of these ocular disorders, many of which are pathologies causing visual impairment, blindness, and subsequent loss of life quality. Studies with nutraceutic supplements in aging eye-related pathologies have also been reviewed. CONCLUSION OS, nutritional status, and nutraceutic supplements have to be considered within the standards of care of older ophthalmologic patients. OS biomarkers and surrogate end points may help in managing the aging population with ocular diseases.
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Affiliation(s)
| | - Roberto Gallego-Pinazo
- Department of Ophthalmology, Macula Section, The University and Polytechnic Hospital La Fe, Valencia, Spain
| | - Jose Javier García-Medina
- Ophthalmic Research Unit “Santiago Grisolía”, Valencia, Spain
- Department of Ophthalmology, University Hospital Reina Sofia, Murcia, Spain
| | - Vicente Zanón-Moreno
- Ophthalmic Research Unit “Santiago Grisolía”, Valencia, Spain
- Faculty of Medicine, University of Valencia, Spain
| | | | - Rosa Dolz-Marco
- Department of Ophthalmology, Macula Section, The University and Polytechnic Hospital La Fe, Valencia, Spain
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Antioxidant drug therapy approaches for neuroprotection in chronic diseases of the retina. Int J Mol Sci 2014; 15:1865-86. [PMID: 24473138 PMCID: PMC3958826 DOI: 10.3390/ijms15021865] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Revised: 01/18/2014] [Accepted: 01/21/2014] [Indexed: 12/31/2022] Open
Abstract
The molecular pathways contributing to visual signal transduction in the retina generate a high energy demand that has functional and structural consequences such as vascularization and high metabolic rates contributing to oxidative stress. Multiple signaling cascades are involved to actively regulate the redox state of the retina. Age-related processes increase the oxidative load, resulting in chronically elevated levels of oxidative stress and reactive oxygen species, which in the retina ultimately result in pathologies such as glaucoma or age-related macular degeneration, as well as the neuropathic complications of diabetes in the eye. Specifically, oxidative stress results in deleterious changes to the retina through dysregulation of its intracellular physiology, ultimately leading to neurodegenerative and potentially also vascular dysfunction. Herein we will review the evidence for oxidative stress-induced contributions to each of the three major ocular pathologies, glaucoma, age-related macular degeneration, and diabetic retinopathy. The premise for neuroprotective strategies for these ocular disorders will be discussed in the context of recent clinical and preclinical research pursuing novel therapy development approaches.
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Grover AK, Samson SE. Antioxidants and vision health: facts and fiction. Mol Cell Biochem 2013; 388:173-83. [PMID: 24311110 DOI: 10.1007/s11010-013-1908-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2013] [Accepted: 11/15/2013] [Indexed: 12/12/2022]
Abstract
A number of nutritional supplements containing antioxidants are advertised for better vision health. Do they benefit the average consumer? The literature was examined for the effectiveness of antioxidants for human eye health, and for the intricacies in collection of such evidence. The following diseases were considered: cataract, glaucoma, age-related macular degeneration (AMD), retinopathy, retinitis pigmentosa, eye infections, and uveitis. The literature indicates that antioxidant supplements plus lutein have a reasonable probability of retarding AMD. For glaucoma, such supplements were ineffectual in some studies but useful in others. In some studies, antioxidant rich fruits and vegetables were also useful for protection against glaucoma. For diabetic retinopathy, antioxidant supplements may have a small benefit, if any, but only as an adjunct to glycemic control. In very high-risk premature retinopathy and retinitis pigmentosa, antioxidant supplements may be beneficial but those with excess Vitamin E should be avoided. For cataract, there is no evidence for an advantage of such nutritional supplements. However, lubricant drops containing N-acetylcarnosine may be helpful in initial stages of the disease. For eye infections and other causes of uveitis, antioxidants have not been found useful. We recommend that a diet high in antioxidant rich foods should be developed as a habit from an early age. However, when initial signs of vision health deterioration are observed, the appropriate nutritional supplement products may be recommended but only to augment the primary medical treatments.
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Affiliation(s)
- Ashok K Grover
- Department of Medicine, McMaster University, Hamilton, ON, L8N3Z5, Canada,
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Galbis-Estrada C, Pinazo-Durán MD, Cantú-Dibildox J, Marco-Ramírez C, Díaz-Llópis M, Benítez-del-Castillo J. Patients undergoing long-term treatment with antihypertensive eye drops responded positively with respect to their ocular surface disorder to oral supplementation with antioxidants and essential fatty acids. Clin Interv Aging 2013; 8:711-9. [PMID: 23818768 PMCID: PMC3693747 DOI: 10.2147/cia.s43191] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Background Glaucoma and dry eye disorders (DEDs) are frequent comorbidities. The antioxidant and anti-inflammatory properties of essential polyunsaturated fatty acids have been extensively studied in relation to eye diseases. Objective Our objective was to determine the effects of oral supplementation with a combined formulation of antioxidants and essential polyunsaturated fatty acids on expression of cytokines and chemokines in tears from patients with DEDs or primary open-angle glaucoma (POAG). Methods Participants (n = 97) were distributed into three groups: (1) individuals with nonsevere DEDs (DEDG), (2) individuals with nonadvanced POAG (POAGG), and (3) healthy controls. These groups were randomized into two subgroups: one received a daily antioxidant and essential polyunsaturated fatty acid supplement (two pills) for 3 months (+S), and the other did not (−NS). Participants were interviewed and ophthalmologically examined. Concentrations of specific cytokines and chemokines in reflex tears were determined by multiplexed particle-based flow cytometry. The data were analyzed statistically (SPSS version 15.0). Results Comparison of the results from the DEDG and POAGG patients showed significant differences in tear expression of granulocyte-macrophage colony-stimulating factor (P = 0.008), tumor necrosis factor α (P = 0.005), vascular endothelial growth factor (P = 0.038), interleukin-4 (P = 0.030), and interleukin-6 (P = 0.044). The main signs and symptoms of dry eyes such as dryness, burning, photophobia, eye heaviness, and blurred vision, as well as positive changes in eyelashes, hair, nails and skin, were significantly improved in DEDG +S and POAGG +S patients relative to unsupplemented patients. Conclusion Inflammation biomarkers were differentially expressed in glaucomatous tears, but the differences changed upon antioxidant/essential polyunsaturated fatty acid supplementation. Chronic instillation of antihypertensive eye drops must be considered for integrating protocols to glaucoma standards of care.
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Affiliation(s)
- Carmen Galbis-Estrada
- Ophthalmic Research Unit Santiago Grisolia, Department of Surgery/Ophthalmology, Faculty of Medicine, University of Valencia, Valencia, Spain
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