scholarly journals Rethinking Nuclear Receptors as Potential Therapeutic Targets for Retinal Diseases

2016 ◽  
Vol 21 (10) ◽  
pp. 1007-1018 ◽  
Author(s):  
Mayur Choudhary ◽  
Goldis Malek
Keyword(s):  
Nuclear Receptors ◽  
Therapeutic Potential ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Metabolic Dysregulation ◽  
Age Related ◽  
Growing Body ◽  
Transcription Regulators ◽  
Key Aspects

Collectively, retinal diseases, including age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy, result in severe vision impairment worldwide. The absence and/or limited availability of successful drug therapies for these blinding disorders necessitates further understanding their pathobiology and identifying new targetable signaling pathways. Nuclear receptors are transcription regulators of many key aspects of human physiology, as well as pathophysiology, with reported roles in development, aging, and disease. Some of the pathways regulated by nuclear receptors include, but are not limited to, angiogenesis, inflammation, and lipid metabolic dysregulation, mechanisms also important in the initiation and development of several retinal diseases. Herein, we present an overview of the biology of three diseases affecting the posterior eye, summarize a growing body of evidence that suggests direct or indirect involvement of nuclear receptors in disease progression, and discuss the therapeutic potential of targeting nuclear receptors for treatment.

scholarly journals Development of a Fundus Image-Based Deep Learning Diagnostic Tool for Various Retinal Diseases

2021 ◽  
Vol 11 (5) ◽  
pp. 321
Author(s):  
Kyoung Min Kim ◽  
Tae-Young Heo ◽  
Aesul Kim ◽  
Joohee Kim ◽  
Kyu Jin Han ◽  
...  
Keyword(s):  
Network Models ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Diagnostic Tools ◽  
Retinal Images ◽  
Dense Layer ◽  
Retinal Diseases ◽  
Fundus Image ◽  
Neural Network Models ◽  
Age Related

Artificial intelligence (AI)-based diagnostic tools have been accepted in ophthalmology. The use of retinal images, such as fundus photographs, is a promising approach for the development of AI-based diagnostic platforms. Retinal pathologies usually occur in a broad spectrum of eye diseases, including neovascular or dry age-related macular degeneration, epiretinal membrane, rhegmatogenous retinal detachment, retinitis pigmentosa, macular hole, retinal vein occlusions, and diabetic retinopathy. Here, we report a fundus image-based AI model for differential diagnosis of retinal diseases. We classified retinal images with three convolutional neural network models: ResNet50, VGG19, and Inception v3. Furthermore, the performance of several dense (fully connected) layers was compared. The prediction accuracy for diagnosis of nine classes of eight retinal diseases and normal control was 87.42% in the ResNet50 model, which added a dense layer with 128 nodes. Furthermore, our AI tool augments ophthalmologist’s performance in the diagnosis of retinal disease. These results suggested that the fundus image-based AI tool is applicable for the medical diagnosis process of retinal diseases.

scholarly journals Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Therapeutic Strategies ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

scholarly journals A Systematic Review of Carotenoids in the Management of Diabetic Retinopathy

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2441
Author(s):  
Drake W. Lem ◽  
Dennis L. Gierhart ◽  
Pinakin Gunvant Davey
Keyword(s):  
Diabetic Retinopathy ◽  
Vision Loss ◽  
Therapeutic Potential ◽  
Microvascular Disease ◽  
Age Related Macular Degeneration ◽  
Cell Degeneration ◽  
Neuroprotective Effects ◽  
Age Related ◽  
Induced Changes ◽  
Dietary Carotenoid

Diabetic retinopathy, which was primarily regarded as a microvascular disease, is the leading cause of irreversible blindness worldwide. With obesity at epidemic proportions, diabetes-related ocular problems are exponentially increasing in the developed world. Oxidative stress due to hyperglycemic states and its associated inflammation is one of the pathological mechanisms which leads to depletion of endogenous antioxidants in retina in a diabetic patient. This contributes to a cascade of events that finally leads to retinal neurodegeneration and irreversible vision loss. The xanthophylls lutein and zeaxanthin are known to promote retinal health, improve visual function in retinal diseases such as age-related macular degeneration that has oxidative damage central in its etiopathogenesis. Thus, it can be hypothesized that dietary supplements with xanthophylls that are potent antioxidants may regenerate the compromised antioxidant capacity as a consequence of the diabetic state, therefore ultimately promoting retinal health and visual improvement. We performed a comprehensive literature review of the National Library of Medicine and Web of Science databases, resulting in 341 publications meeting search criteria, of which, 18 were found eligible for inclusion in this review. Lutein and zeaxanthin demonstrated significant protection against capillary cell degeneration and hyperglycemia-induced changes in retinal vasculature. Observational studies indicate that depletion of xanthophyll carotenoids in the macula may represent a novel feature of DR, specifically in patients with type 2 or poorly managed type 1 diabetes. Meanwhile, early interventional trials with dietary carotenoid supplementation show promise in improving their levels in serum and macular pigments concomitant with benefits in visual performance. These findings provide a strong molecular basis and a line of evidence that suggests carotenoid vitamin therapy may offer enhanced neuroprotective effects with therapeutic potential to function as an adjunct nutraceutical strategy for management of diabetic retinopathy.

scholarly journals Pharmaceutical Induction of PGC-1α Promotes Retinal Pigment Epithelial Cell Metabolism and Protects against Oxidative Damage

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Sangeeta Satish ◽  
Hannah Philipose ◽  
Mariana Aparecida Brunini Rosales ◽  
Magali Saint-Geniez
Keyword(s):  
Cell Death ◽  
Antioxidant Enzymes ◽  
Oxidative Damage ◽  
Therapeutic Potential ◽  
Retinal Pigment Epithelial Cell ◽  
Cell Metabolism ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Age Related

Retinal pigment epithelium (RPE) dysfunction due to accumulation of reactive oxygen species and oxidative damage is a key event in the development of age-related macular degeneration (AMD). Here, we examine the therapeutic potential of ZLN005, a selective PGC-1α transcriptional regulator, in protecting RPE from cytotoxic oxidative damage. Gene expression analysis on ARPE-19 cells treated with ZLN005 shows robust upregulation of PGC-1α and its associated transcription factors, antioxidant enzymes, and mitochondrial genes. Energetic profiling shows that ZLN005 treatment enhances RPE mitochondrial function by increasing basal and maximal respiration rates, and spare respiratory capacity. In addition, ZLN005 robustly protects ARPE-19 cells from cell death caused by H2O2, ox-LDL, and NaIO3 without exhibiting any cytotoxicity under basal conditions. ZLN005 protection against H2O2-mediated cell death was lost in PGC-1α-silenced cells. Our data indicates that ZLN005 efficiently protects RPE cells from oxidative damage through selective induction of PGC-1α and its target antioxidant enzymes. ZLN005 may serve as a novel therapeutic agent for retinal diseases associated with RPE dystrophies.

scholarly journals Potential Treatment of Retinal Diseases with Iron Chelators

2018 ◽  
Vol 11 (4) ◽  
pp. 112 ◽  
Author(s):  
Wanting Shu ◽  
Joshua Dunaief
Keyword(s):  
Retinal Degeneration ◽  
Therapeutic Potential ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Hereditary Diseases ◽  
Iron Chelators ◽  
Excess Iron ◽  
Age Related

Iron is essential for life, while excess iron can be toxic. Iron generates hydroxyl radical, which is the most reactive free radical, causing oxidative stress. Since iron is absorbed through the diet but not excreted from the body, it accumulates with age in tissues, including the retina, consequently leading to age-related toxicity. This accumulation is further promoted by inflammation. Hereditary diseases such as aceruloplasminemia, Friedreich’s ataxia, pantothenate kinase-associated neurodegeneration, and posterior column ataxia with retinitis pigmentosa involve retinal degeneration associated with iron dysregulation. In addition to hereditary causes, dietary or parenteral iron supplementation has been recently reported to elevate iron levels in the retinal pigment epithelium (RPE) and promote retinal degeneration. Ocular siderosis from intraocular foreign bodies or subretinal hemorrhage can also lead to retinopathy. Evidence from mice and humans suggests that iron toxicity may contribute to age-related macular degeneration pathogenesis. Iron chelators can protect photoreceptors and RPE in various mouse models. The therapeutic potential for iron chelators is under investigation.

scholarly journals Review of Subthreshold Diode Micropulse Laser Treatment for Retinal Diseases

2018 ◽  
Vol 1 (1) ◽  
pp. 62-70
Author(s):  
Juhn AT ◽  
Shyu AP ◽  
Benjamin J ◽  
Zhang Y
Keyword(s):  
Diabetic Retinopathy ◽  
Treatment Modality ◽  
Branch Retinal Vein Occlusion ◽  
Age Related Macular Degeneration ◽  
Clinical Settings ◽  
Retinal Diseases ◽  
Micropulse Laser ◽  
Vein Occlusion ◽  
Age Related ◽  
New Treatment

Subthreshold Diode Micropulse (SDM) laser is a relatively new treatment modality that confers very little to no anatomical risk to the retina. However, its efficacy is still being studied, and the scenario where SDM is most useful is still being elucidated. This paper reviews articles from 1997 to 2017 and reviews the settings, results, and outcomes of SDM in various clinical settings including diabetic macular edema, branch retinal vein occlusion, central serous Chorioretinopathy, proliferative diabetic retinopathy, and age-related macular degeneration.

scholarly journals Prevalence and causes of vision loss in North Africa and Middle East in 2015: magnitude, temporal trends and projections

2018 ◽  
Vol 103 (7) ◽  
pp. 863-870 ◽  
Author(s):  
Rim Kahloun ◽  
Moncef Khairallah ◽  
Serge Resnikoff ◽  
Maria Vittoria Cicinelli ◽  
Seth R Flaxman ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Middle East ◽  
North Africa ◽  
Refractive Error ◽  
Vision Loss ◽  
Corneal Opacity ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Uncorrected Refractive Error

BackgroundTo assess the prevalence and causes of vision impairment in North Africa and the Middle East (NAME) from 1990 to 2015 and to forecast projections for 2020.MethodsBased on a systematic review of medical literature, the prevalence of blindness (presenting visual acuity (PVA) <3/60 in the better eye), moderate and severe vision impairment (MSVI; PVA <6/18 but ≥3/60) and mild vision impairment (PVA <6/12 but ≥6/18) was estimated for 2015 and 2020.ResultsThe age-standardised prevalence of blindness and MSVI for all ages and genders decreased from 1990 to 2015, from 1.72 (0.53–3.13) to 0.95% (0.32%–1.71%), and from 6.66 (3.09–10.69) to 4.62% (2.21%–7.33%), respectively, with slightly higher figures for women than men. Cataract was the most common cause of blindness in 1990 and 2015, followed by uncorrected refractive error. Uncorrected refractive error was the leading cause of MSVI in the NAME region in 1990 and 2015, followed by cataract. A reduction in the proportions of blindness and MSVI due to cataract, corneal opacity and trachoma is predicted by 2020. Conversely, an increase in the proportion of blindness attributable to uncorrected refractive error, glaucoma, age-related macular degeneration and diabetic retinopathy is expected.ConclusionsIn 2015 cataract and uncorrected refractive error were the major causes of vision loss in the NAME region. Proportions of vision impairment from cataract, corneal opacity and trachoma are expected to decrease by 2020, and those from uncorrected refractive error, glaucoma, diabetic retinopathy and age-related macular degeneration are predicted to increase by 2020.

scholarly journals Antioxidant Role of PRGF on RPE Cells after Blue Light Insult as a Therapy for Neurodegenerative Diseases

2020 ◽  
Vol 21 (3) ◽  
pp. 1021 ◽  
Author(s):  
Carlota Suárez-Barrio ◽  
Susana del Olmo-Aguado ◽  
Eva García-Pérez ◽  
María de la Fuente ◽  
Francisco Muruzabal ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Human Cell Line ◽  
Antioxidant Effect ◽  
Age Related Macular Degeneration ◽  
Strong Impact ◽  
Retinal Diseases ◽  
Age Related ◽  
Gene And Protein Expression

Oxidative stress has a strong impact on the development of retinal diseases such as age-related macular degeneration (AMD). Plasma rich in growth factors (PRGF) is a novel therapeutic approach in ophthalmological pathologies. The aim of this study was to analyze the antioxidant effect of PRGF in retinal epithelial cells (EPR) in in vitro and ex vivo retinal phototoxicity models. In vitro analyses were performed on ARPE19 human cell line. Viability and mitochondrial status were assessed in order to test the primary effects of PRGF. GSH level, and protein and gene expression of the main antioxidant pathway (Keap1, Nrf2, GCL, HO-1, and NQO1) were also studied. Ex vivo analyses were performed on rat RPE, and HO-1 and Nrf2 gene and protein expression were evaluated. The results show that PRGF reduces light insult by stimulating the cell response against oxidative damage and modulates the antioxidant pathway. We conclude that PRGF’s protective effect could prove useful as a new therapy for treating neurodegenerative disorders such as AMD.

scholarly journals Neuroprotective Potential of Ginkgo biloba in Retinal Diseases

Planta Medica ◽  
2019 ◽  
Vol 85 (17) ◽  
pp. 1292-1303 ◽  
Author(s):  
Isabel Martínez-Solís ◽  
Nuria Acero ◽  
Francisco Bosch-Morell ◽  
Encarna Castillo ◽  
María Eugenia González-Rosende ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ginkgo Biloba ◽  
Redox Homeostasis ◽  
Antioxidant Properties ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Age Related ◽  
The Central Nervous System ◽  
Degenerative Processes

AbstractLike other tissues of the central nervous system, the retina is susceptible to damage by oxidative processes that result in several neurodegenerative disease such as age-related macular degeneration, diabetic retinopathy, glaucoma, ischaemic retinal disease, retinal disease produced by light oxidation, and detached retina, among other diseases. The use of antioxidant substances is a solution to some health problems caused by oxidative stress, because they regulate redox homeostasis and reduce oxidative stress. This is important for neurodegeneration linked to oxidation processes. In line with this, Ginkgo biloba is a medicinal plant with excellent antioxidant properties whose effects have been demonstrated in several degenerative processes, including retinal diseases associated with neurodegeneration. This review describes the current literature on the role of ginkgo in retinal diseases associated with neurodegeneration. The information leads to the conclusion that G. biloba extracts might be a good option to improve certain neurodegenerative retinal diseases, but more research is needed to determine the safety and efficacy of G. biloba in these retinal degenerative processes.

scholarly journals Prevalence and causes of vision loss in East Asia in 2015: magnitude, temporal trends and projections

2019 ◽  
Vol 104 (5) ◽  
pp. 616-622 ◽  
Author(s):  
Ching-Yu Cheng ◽  
Ningli Wang ◽  
Tien Y Wong ◽  
Nathan Congdon ◽  
Mingguang He ◽  
...  
Keyword(s):  
Visual Acuity ◽  
East Asia ◽  
Macular Degeneration ◽  
Refractive Error ◽  
Temporal Trends ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Public Healthcare ◽  
Age Related ◽  
Uncorrected Refractive Error

BackgroundTo determine the prevalence and causes of blindness and vision impairment (VI) in East Asia in 2015 and to forecast the trend to 2020.MethodsThrough a systematic literature review and meta-analysis, we estimated prevalence of blindness (presenting visual acuity <3/60 in the better eye), moderate-to-severe vision impairment (MSVI; 3/60≤presenting visual acuity <6/18), mild vision impairment (mild VI: 6/18≤presenting visual acuity <6/12) and uncorrected presbyopia for 1990, 2010, 2015 and 2020. A total of 44 population-based studies were included.ResultsIn 2015, age-standardised prevalence of blindness, MSVI, mild VI and uncorrected presbyopia was 0.37% (80% uncertainty interval (UI) 0.12%–0.68%), 3.06% (80% UI 1.35%–5.16%) and 2.65% (80% UI 0.92%–4.91%), 32.91% (80% UI 18.72%–48.47%), respectively, in East Asia. Cataract was the leading cause of blindness (43.6%), followed by uncorrected refractive error (12.9%), glaucoma, age-related macular degeneration, corneal diseases, trachoma and diabetic retinopathy (DR). The leading cause for MSVI was uncorrected refractive error, followed by cataract, age-related macular degeneration, glaucoma, corneal disease, trachoma and DR. The burden of VI due to uncorrected refractive error, cataracts, glaucoma and DR has continued to rise over the decades reported.ConclusionsAddressing the public healthcare barriers for cataract and uncorrected refractive error can help eliminate almost 57% of all blindness cases in this region. Therefore, public healthcare efforts should be focused on effective screening and effective patient education, with access to high-quality healthcare.

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