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Malepati A, Grant MB. The Role and Diagnostic Potential of Insulin-like Growth Factor 1 in Diabetic Retinopathy and Diabetic Macular Edema. Int J Mol Sci 2025; 26:3961. [PMID: 40362202 PMCID: PMC12072156 DOI: 10.3390/ijms26093961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2025] [Revised: 04/11/2025] [Accepted: 04/18/2025] [Indexed: 05/15/2025] Open
Abstract
Diabetes mellitus (DM) is a chronic metabolic disorder that results in hyperglycemia, leading to multiple microvascular and macrovascular complications, including significant ocular damage resulting in the development of diabetic retinopathy (DR) and diabetic macular edema (DME). Many factors contribute to the pathogenesis of DR and DME, including hyperglycemia-mediated vascular and neuronal abnormalities and local and systemic inflammation. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been implicated in the initiation and progression of DR and DME through a variety of mechanistic processes. In this review, we provide a comprehensive synopsis of the diverse roles and molecular pathways supporting IGF-1 in the pathogenesis of DR and DME, elucidating its range of effects from detrimental to protective, depending on the context and stage of disease. We further investigate the underlying inflammatory processes regulated by IGF-1 and examine how the interaction of IGF-1 with key signaling molecules influences these inflammatory mechanisms. Additionally, the potential of serum IGF-1 as a biomarker for the progression of DR and DME in clinical practice is discussed. Finally, we consider current therapeutic approaches for DR and DME in relation to IGF-1 and explore novel therapeutic targets and innovative delivery methods. By providing an in-depth understanding of IGF-1's role in the pathogenesis and progression of DR and DME, this review underscores the diagnostic utility of serum IGF-1 and puts forth new treatment strategies to improve the management of DR and DME.
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Affiliation(s)
- Akanksha Malepati
- UAB Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA;
| | - Maria B. Grant
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35233, USA
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Fang Y, Wang Q, Li Y, Zeng L, Liu J, Ou K. On implications of somatostatin in diabetic retinopathy. Neural Regen Res 2024; 19:1984-1990. [PMID: 38227526 DOI: 10.4103/1673-5374.390955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Accepted: 10/10/2023] [Indexed: 01/17/2024] Open
Abstract
Somatostatin, a naturally produced neuroprotective peptide, depresses excitatory neurotransmission and exerts anti-proliferative and anti-inflammatory effects on the retina. In this review, we summarize the progress of somatostatin treatment of diabetic retinopathy through analysis of relevant studies published from February 2019 to February 2023 extracted from the PubMed and Google Scholar databases. Insufficient neuroprotection, which occurs as a consequence of declined expression or dysregulation of retinal somatostatin in the very early stages of diabetic retinopathy, triggers retinal neurovascular unit impairment and microvascular damage. Somatostatin replacement is a promising treatment for retinal neurodegeneration in diabetic retinopathy. Numerous pre-clinical and clinical trials of somatostatin analog treatment for early diabetic retinopathy have been initiated. In one such trial (EUROCONDOR), topical administration of somatostatin was found to exert neuroprotective effects in patients with pre-existing retinal neurodysfunction, but had no impact on the onset of diabetic retinopathy. Overall, we concluded that somatostatin restoration may be especially beneficial for the growing population of patients with early-stage retinopathy. In order to achieve early prevention of diabetic retinopathy initiation, and thereby salvage visual function before the appearance of moderate non-proliferative diabetic retinopathy, several issues need to be addressed. These include the needs to: a) update and standardize the retinal screening scheme to incorporate the detection of early neurodegeneration, b) identify patient subgroups who would benefit from somatostatin analog supplementation, c) elucidate the interactions of somatostatin, particularly exogenously-delivered somatostatin analogs, with other retinal peptides in the context of hyperglycemia, and d) design safe, feasible, low cost, and effective administration routes.
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Affiliation(s)
- Yanhong Fang
- Department of Ophthalmology, Chongqing University Jiangjin Hospital, Chongqing, China
| | - Qionghua Wang
- Department of Ophthalmology, Chongqing University Jiangjin Hospital, Chongqing, China
| | - Youjian Li
- College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, IATTI, Chongqing University of Arts and Sciences, Chongqing, China
| | - Li Zeng
- Shandong Provincial Hospital, Shandong Laboratory Animal Center, Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Jian Liu
- Academic Unit of Ophthalmology, Bristol Medical School, University of Bristol, Bristol, UK
| | - Kepeng Ou
- College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, IATTI, Chongqing University of Arts and Sciences, Chongqing, China
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Zhang X, Wang H, Zhang K, Ma J, He H, Song S, Shao E, Chen B, Yang J, Zhao X, Sui W, Wang M, Liu S, Guo X, Zhu H, Yao Y, Zhong Y, Xing B. Blood Glucose Levels Moderate the Associations Between IGF-1 Levels and Choroidal Metrics in Patients With Diabetes With Acromegaly Without Diabetic Retinopathy. Transl Vis Sci Technol 2024; 13:20. [PMID: 39078643 PMCID: PMC11290567 DOI: 10.1167/tvst.13.7.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 06/21/2024] [Indexed: 07/31/2024] Open
Abstract
Purpose To examine the effects of serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) on choroidal structures with different blood glucose levels in patients with diabetes mellitus (DM) with acromegaly without diabetic retinopathy. Methods Eighty-eight eyes of 44 patients with acromegaly were divided into a nondiabetic group (23 patients, 46 eyes) and a diabetic group (21 patients, 42 eyes). Forty-four age- and sex-matched healthy controls and 21 patients with type 2 DM without diabetic retinopathy were also included. Linear regression models with a simple slope analysis were used to identify the correlation and interaction between endocrine parameters and choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascular index (CVI). Results Our study revealed significant increases in the ChT, LA, SA, and TCA in patients with acromegaly compared with healthy controls, with no difference in the CVI. Comparatively, patients with DM with acromegaly had greater ChT than matched patients with type 2 DM, with no significant differences in other choroidal parameters. The enhancement of SA, LA and TCA caused by an acromegalic status disappeared in patients with diabetic status, whereas ChT and CVI were not affected by the interaction. In the diabetic acromegaly, higher IGF-1 (P = 0.006) and GH levels (P = 0.049), longer DM duration (P = 0.007), lower blood glucose (P = 0.001), and the interaction between GH and blood glucose were associated independently with thicker ChT. Higher GH levels (P = 0.016, 0.004 and 0.007), longer DM duration (P = 0.022, 0.013 and 0.013), lower blood glucose (P = 0.034, 0.011 and 0.01), and the interaction of IGF-1 and blood glucose were associated independently with larger SA, LA, and TCA. As blood glucose levels increased, the positive correlation between serum GH level and ChT diminished, and became insignificant when blood glucose was more than 7.35 mM/L. The associations between serum IGF-1 levels and LA, SA, and TCA became increasingly negative, with LA, becoming significantly and negatively associated to the GH levels only when blood glucose levels were more than 8.59 mM/L. Conclusions Acromegaly-related choroidal enhancements diminish in the presence of DM. In diabetic acromegaly, blood glucose levels are linked negatively with changes in choroidal metrics and their association with GH and IGF-1. Translational Relevance We revealed the potential beneficial impacts of IGF-1 and GH on structural measures of the choroid in patients with DM at relatively well-controlled blood glucose level, which could provide a potential treatment target for diabetic retinopathy.
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Affiliation(s)
- Xia Zhang
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Neurosurgery, Pituitary Tumour Center of Excellence, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Heng Wang
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Kai Zhang
- Chongqing Chang'an Industrial Group Co., Ltd, Chongqing, China
| | - Jin Ma
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Neurosurgery, Pituitary Tumour Center of Excellence, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huijing He
- Department of Epidemiology and Statistics, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuang Song
- Center for Statistical Science, Department of Industrial Engineering, Tsinghua University, Beijing, China
| | - Enhua Shao
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bo Chen
- Department of Neurology, Tongji Hospital of Tongji Medical College, Huazhong University of Science of Technology, Wuhan, China
| | - Jingyuan Yang
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinyu Zhao
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Key Laboratory of Ocular Fundus Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenda Sui
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Meng Wang
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sihua Liu
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaopeng Guo
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huijuan Zhu
- Department of Neurosurgery, Pituitary Tumour Center of Excellence, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yong Yao
- Department of Neurosurgery, Pituitary Tumour Center of Excellence, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yong Zhong
- Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Neurosurgery, Pituitary Tumour Center of Excellence, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bing Xing
- Department of Neurosurgery, Pituitary Tumour Center of Excellence, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Thabet RA, Sherif EM, ElAal AOA, Mahmoud RA. Insulin-like growth factor 1 and sex hormones for assessment of anthropometric and pubertal growth of Egyptian children and adolescents with type 1 diabetes mellitus (single center study). BMC Endocr Disord 2024; 24:62. [PMID: 38724932 PMCID: PMC11080226 DOI: 10.1186/s12902-024-01596-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 05/02/2024] [Indexed: 05/13/2024] Open
Abstract
BACKGROUND This study aimed to assess the anthropometric measures and pubertal growth of children and adolescents with Type 1 diabetes mellitus (T1DM) and to detect risk determinants affecting these measures and their link to glycemic control. PATIENTS AND METHODS Two hundred children and adolescents were assessed using anthropometric measurements. Those with short stature were further evaluated using insulin-like growth factor 1 (IGF-1), bone age, and thyroid profile, while those with delayed puberty were evaluated using sex hormones and pituitary gonadotropins assay. RESULTS We found that 12.5% of our patients were short (height SDS < -2) and IGF-1 was less than -2 SD in 72% of them. Patients with short stature had earlier age of onset of diabetes, longer duration of diabetes, higher HbA1C and urinary albumin/creatinine ratio compared to those with normal stature (p < 0.05). Additionally, patients with delayed puberty had higher HbA1c and dyslipidemia compared to those with normal puberty (p < 0.05). The regression analysis revealed that factors associated with short stature were; age at diagnosis, HbA1C > 8.2, and albumin/creatinine ratio > 8 (p < 0.05). CONCLUSION Children with uncontrolled T1DM are at risk of short stature and delayed puberty. Diabetes duration and control seem to be independent risk factors for short stature.
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Affiliation(s)
- Rasha A Thabet
- Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
| | - Eman M Sherif
- Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | | | - Rana A Mahmoud
- Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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Puddu A, Maggi DC. Klotho: A new therapeutic target in diabetic retinopathy? World J Diabetes 2023; 14:1027-1036. [PMID: 37547589 PMCID: PMC10401458 DOI: 10.4239/wjd.v14.i7.1027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 05/12/2023] [Accepted: 05/22/2023] [Indexed: 07/12/2023] Open
Abstract
Klotho (Kl) is considered an antiaging gene, mainly for the inhibition of the insulin-like growth factor-1 signaling. Kl exists as full-length transmembrane, which acts as co-receptor for fibroblast growth factor receptor, and in soluble forms (sKl). The sKl may exert pleiotropic effects on organs and tissues by regulating several pathways involved in the pathogenesis of diseases associated with oxidative and inflammatory state. In diabetic Patients, serum levels of Kl are significantly decreased compared to healthy subjects, and are related to duration of diabetes. In diabetic retinopathy (DR), one of the most common microvascular complications of type 2 diabetes, serum Kl levels are negatively correlated with progression of the disease. A lot of evidences showed that Kl regulates several mechanisms involved in maintaining homeostasis and functions of retinal cells, including phagocytosis, calcium signaling, secretion of vascular endothelial growth factor A (VEGF-A), maintenance of redox status, and melanin biosynthesis. Experimental data have been shown that Kl exerts positive effects on several mechanisms involved in onset and progression of DR. In particular, treatment with Kl: (1) Prevents apoptosis induced by oxidative stress in human retinal endothelial cells and in retinal pigment epithelium (RPE) cells; (2) reduces secretion of VEGF-A by RPE cells; and (3) decreases subretinal fibrosis and preserves autophagic activity. Therefore, Kl may become a novel biomarker and a good candidate for the treatment of DR.
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Affiliation(s)
- Alessandra Puddu
- Department of Internal Medicine and Medical Specialties, University of Genova, Genova 16132, Italy
| | - Davide Carlo Maggi
- Department of Internal Medicine and Medical Specialties, University of Genova, Genova 16132, Italy
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Du H, Xia J, Huang L, Zheng L, Gu W, Yi F. Relationship between insulin-like growth factor-1 and cerebral small vessel disease and its mechanisms: advances in the field. Front Aging Neurosci 2023; 15:1190869. [PMID: 37358957 PMCID: PMC10285072 DOI: 10.3389/fnagi.2023.1190869] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 05/23/2023] [Indexed: 06/28/2023] Open
Abstract
Insulin-like growth factor-1 (IGF-1) is an active polypeptide protein that closely resembles the structural sequence of insulin and is involved in a variety of metabolic processes in the body. Decreased IGF-1 circulation levels are associated with an increased risk of stroke and a poorer prognosis, but the relationship with cerebral small vessel disease (cSVD) is unclear. Some studies found that the level of IGF-1 in patients with cSVD was significantly reduced, but the clinical significance and underlying mechanisms are unknown. This article reviews the correlation between IGF-1 and cerebrovascular disease and explores the potential relationship and mechanism between IGF-1 and cSVD.
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Affiliation(s)
- Hao Du
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jian Xia
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Cerebrovascular Disease of Hunan Province, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Lei Huang
- Department of Rehabilitation, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China
| | - Lan Zheng
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Wenping Gu
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Cerebrovascular Disease of Hunan Province, Central South University, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Fang Yi
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Department of Geriatric Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China
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Yang N, Li MX, Peng XY. Effects of intensive insulin therapy on the retinal microvasculature in patients with type 2 diabetes mellitus: a prospective observational study. BMC Ophthalmol 2022; 22:187. [PMID: 35459162 PMCID: PMC9034536 DOI: 10.1186/s12886-022-02397-9] [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: 01/21/2022] [Accepted: 04/11/2022] [Indexed: 12/22/2022] Open
Abstract
Background We examined the retinal microvascular changes and associated factors in type 2 diabetes mellitus (T2DM) before and after intensive insulin therapy. Methods This prospective observational study recruited patients with T2DM and divided them into intensive insulin therapy and oral hypoglycemic agent groups. All patients enrolled in this study had diabetes without retinopathy or non-proliferative diabetic retinopathy. Optical coherence tomography angiography (OCTA) was used in all patients before treatment and at 1, 3, and 6 months after treatment. Vessel density (VD) and thickness changes in the macular and optic disc areas were assessed. Results The study included 36 eyes in the intensive insulin therapy group and 36 in the oral hypoglycemic agent group. One month after treatment, VD in the deep capillary plexus (DCP) and peripapillary capillary VD (ppVD) were significantly decreased by intensification (P = 0.009, 0.000). At three months after treatment, decreases in VD induced by intensification were found in the superficial capillary plexus (SCP), DCP, foveal density in a 300-μm-wide region around the foveal avascular area (FD-300), and ppVD (P = 0.032, 0.000, 0.039, 0.000). Six months after treatment, decreases in VD by intensification were observed in the DCP and ppVD groups (P = 0.000, 0.000). Vessel density showed no significant change in the oral hypoglycemic agent group after treatment. The amount of DCP-VD reduction was correlated with macular thickening (r = 0.348, P = 0.038; r = 0.693, P = 0.000 and r = 0.417, P = 0.011, respectively) after intensive insulin therapy. Conclusions Insulin-intensive treatment caused a transient reduction in vessel density in the macular and optic disc areas. DCP-VD and ppVD were more susceptible at an earlier stage. Retinal microvasculature monitoring using OCTA is vital for patients with type 2 diabetes receiving intensive insulin therapy. Supplementary Information The online version contains supplementary material available at 10.1186/s12886-022-02397-9.
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Affiliation(s)
- Ning Yang
- Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Science Key Laboratory, No.17 Hougou Lane, Chongnei Street, Beijing, 100005, China.,Department of Ophthalmology, The Affiliated Hospital of Xuzhou Medical University, Quanshan District, 99 West Huaihai RdJiangsu, Xuzhou, 221002, China
| | - Ming-Xin Li
- Department of Ophthalmology, The Affiliated Hospital of Xuzhou Medical University, Quanshan District, 99 West Huaihai RdJiangsu, Xuzhou, 221002, China
| | - Xiao-Yan Peng
- Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Science Key Laboratory, No.17 Hougou Lane, Chongnei Street, Beijing, 100005, China.
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Lokman Hakim NYDB, Noble S, Thomas NV, Geegana Gamage BS, Maxwell GK, Govindasamy V, Then KY, Das AK, Cheong SK. Genetic Modification as a New Approach to Ameliorate the Therapeutic Efficacy of Stem Cells in Diabetic Retinopathy. Eur J Ophthalmol 2022; 32:11206721211073430. [PMID: 35037488 DOI: 10.1177/11206721211073430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Over the last decades, the strategy of using stem cells has gained a lot of attention in treating many diseases. Recently, DR was identified as one of the common complications experienced by diabetic patients around the world. The current treatment strategy needs to be addressed since the active progression of DR may lead to permanent blindness. Interestingly, varieties of stem cells have emerged to optimize the therapeutic effects. It is also known that stem cells possess multilineage properties and are capable of differentiating, expanding in vitro and undergoing genetic modification. Moreover, modified stem cells have shown to be an ideal resource to prevent the degenerative disease and exhibit promising effects in conferring the migratory, anti-apoptotic, anti-inflammatory and provide better homing for cells into the damaged tissue or organ as well promoting healing properties. Therefore, the understanding of the functional properties of the stem cells may provide the comprehensive guidance to understand the manipulation of stem cells making them useful for long-term therapeutic applications. Hence in this review the potential use and current challenges of genetically modified stem cells to treat DR will be discussed along with its future perspectives.
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Affiliation(s)
| | - Steven Noble
- CryoCord Sdn Bhd, Bio-X Centre, Cyberjaya, Selangor, Malaysia
| | | | | | | | | | - Kong-Yong Then
- CryoCord Sdn Bhd, Bio-X Centre, Cyberjaya, Selangor, Malaysia
- Brighton Healthcare (Bio-X Healthcare Sdn Bhd), Bio-X Centre, Cyberjaya, Selangor, Malaysia
| | - Anjan Kumar Das
- Department of Surgery, 483702IQ City Medical College, Durgapur, West Bengal, India
| | - Soon-Keng Cheong
- Faculty of Medicine & Health Sciences, 65287Universiti Tunku Abdul Rahman (UTAR), Kajang, Selangor, Malaysia
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Koca SB, Akdogan M, Koca S. Evaluation of early retinal vascular changes by optical coherence tomography angiography in children with type 1 diabetes mellitus without diabetic retinopathy. Int Ophthalmol 2021; 42:423-433. [PMID: 34625889 DOI: 10.1007/s10792-021-02059-7] [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: 04/24/2021] [Accepted: 09/21/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE To evaluate macular and peripapillary vascular changes by optical coherence tomography angiography (OCTA) in children with type 1 diabetes mellitus (T1DM) without diabetic retinopathy (DR). METHODS This study included 46 patients with T1DM and 46 age-sex matched healthy subjects. All participants were evaluated in terms of macular and optic disk parameters by using AngioVue. Foveal avascular zone (FAZ) area, macular and optic disk vessel density (VD) were analyzed. The correlation of these parameters with metabolic factors such as disease duration, mean hemoglobin A1c (HbA1c), insulin-like growth factor 1 (IGF-1) standard deviation score (SDS), homocysteine (Hcy) level, body mass index (BMI) SDS and daily insulin dose was also investigated in T1DM group. RESULTS No significant difference was found in FAZ area and optic disk radial peripapillary capillary (RPC) VD comparing diabetic and control groups. In all macular regions, VD was significantly lower in T1DM versus control group both in superficial capillary plexus (SCP) and deep capillary plexus (DCP). None of the metabolic parameters was correlated with FAZ area and optic disk RPC-VD. Vascular density in SCP was negatively correlated with mean HbA1c and positively correlated with IGF-1 SDS. Homocysteine level was negatively correlated with DCP-VD in all areas. CONCLUSION In children with T1DM without clinically apparent DR, VD in SCP and DCP was decreased and OCTA is a valuable imaging technique for detecting early vascular changes. The metabolic parameters such as mean HbA1c, IGF-1 SDS and Hcy affect the macular VD in diabetic children. TRIAL REGISTRATION NUMBER 2011-KAEK-2, 2021/4, Trial registration date: 02.04.2021.
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Affiliation(s)
- Serkan Bilge Koca
- Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey
| | - Muberra Akdogan
- Faculty of Medicine, Department of Ophthalmology, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey
| | - Semra Koca
- Faculty of Medicine, Department of Ophthalmology, Afyonkarahisar Health Sciences University, Afyonkarahisar, Turkey. .,, 1444. Sokak Kandilli Konakları D Blok 2/8, Afyonkarahisar, Türkiye.
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El-Sehrawy AA, Elkhamisy EM, Amani E Badawi, Elshahawy HA, Elsayed E, Mohammed NT, El-Eshmawy MM. Subclinical Hypothyroidism in Patients with Diabetic Retinopathy: Role of Vascular Endothelial Growth Factor. Endocr Metab Immune Disord Drug Targets 2021; 22:502-509. [PMID: 34370652 DOI: 10.2174/1871530321666210809151258] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 06/10/2021] [Accepted: 06/15/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Considering the vital role of vascular endothelial growth factor (VEGF) in the development of diabetic retinopathy (DR) in one hand and the frequent association between subclinical hypothyroidism (SCH) and DR on the other hand. OBJECTIVE The present study was proposed to explore the possible role of VEGF in the relation between SCH and DR, thus we investigated the relation between SCH and VEGF levels in patients with DR. METHODS Two hundred patients with DR were recruited in this study [100 patients with proliferative diabetic retinopathy (PDR) and 100 patients with non-proliferative diabetic retinopathy (NPDR)]. Patients with DR were divided into 2 groups according to thyroid function: patients with SCH or those with euthyroidism. Patients were subjected to careful history taking, and underwent clinical and ophthalmological examination. Fasting blood glucose, glycosylated hemoglobin, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), TSH, FT4, FT3, VEGF and thyroid volume were assessed Results: Among all the studied patients, 21.5% (43/200) had SCH. DR patients with SCH had higher age, diabetes duration, HbA1c, HOMA-IR and VEGF than those with euthyroidism. The frequency of PDR in patients with SCH was 72.1% (31/43) and 43.9% (69/157) in those with euthyroidism, whereas the frequency of NPDR in patients with SCH was 27.9 (12/43) and 56.1% (88/157) in those with euthyroidism (P < 0.003). In multivariate analysis, PDR, HOMA-IR and VEGF levels were the significant predictor variables of SCH. CONCLUSIONS Increased VEGF levels may be implicated in the relationship between SCH and DR.
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Affiliation(s)
- Amr Ali El-Sehrawy
- Department of Internal Medicine, Mansoura Specialized Medical Hospital, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Enas M Elkhamisy
- Department of Internal Medicine, Mansoura Specialized Medical Hospital, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Amani E Badawi
- Department of Ophthalmology, Mansoura Ophthalmic Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Heba A Elshahawy
- Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Eman Elsayed
- Department of Clinical Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Nehal Tharwat Mohammed
- Department of Diagnostic Radiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mervat M El-Eshmawy
- Department of Internal Medicine, Mansoura Specialized Medical Hospital, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Zhao Y, Xiong Z, Chen Y, Wang G, Zhao Y. Activation of Insulin-Like Growth Factor-2 Ameliorates Retinal Cell Damage and Exerts Protection in in vitro Model of Diabetic Retinopathy. Neuroimmunomodulation 2021; 28:266-275. [PMID: 33951651 DOI: 10.1159/000515662] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 03/02/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The major event in the development of diabetes-related blindness and vision impairment is the onset of retinal cell damage. Overall awareness of insulin-like growth factor-2 (IGF2) mechanisms emphasizes its protective behavior in retinal cells that help to provide new information about the development of treatment for retinal complications. OBJECTIVES This study analyzes the effect of in vitro changes associated with the cell survival and rescue mechanism in IGF2 inhibition and activation using chromeceptin and IGF2 peptides in ARPE-19 cells cultured in high glucose conditions. METHOD Cell death was induced using high glucose (15 mmol/L), IGF2 inhibition was done using chromeceptin (1 µM) (Sigma Aldrich, Saint Louis, MO, USA), and IGF2 activation was done using IGF2 peptide (10 ng/mL). The cells were analyzed for changes in cell proliferation, apoptosis markers, antioxidant molecules, and alteration of cytokines. RESULTS The study demonstrated that cells lacking IGF2 exhibited a significant increase in reactive oxygen levels with apoptosis patterns. Also, gene expression analysis by qRT-PCR demonstrated a significant increase in Yes-associated protein 1, CDK2, TNF-α, and BIRC5 genes in cells under high glucose stress and IGF inhibition compared to control. Further, the cytokine analysis also revealed that cells devoid of IGF2 activated an increase in cytokines such as IL-8, CX43, ICAM-1, IL-17, CCL3, and MCP-1 and decreased paraoxonase compared to normal control cells. On the other hand, ARPE-19 cells grown in high glucose shows that IGF2 increases the survival genes with reduced levels of inflammatory cytokines. CONCLUSION The finding of the investigation, therefore, shows that the use of IGF2 activators may prevent the progression of ocular dysfunction in the control of diabetes-related complications.
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Affiliation(s)
- Yantao Zhao
- Department of Ophthalmology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhaohui Xiong
- Department of Ophthalmology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yuping Chen
- Department of Ophthalmology, People's Hospital of Gaoqing County, Zibo City, China
| | - Guoqiang Wang
- Department of Ophthalmology, The First Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yan Zhao
- Department of Ophthalmology, The First Hospital of Hebei Medical University, Shijiazhuang, China
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