Melatonin: Implications for Ocular Disease and Therapeutic Potential

2019 ◽  
Vol 25 (39) ◽  
pp. 4185-4191 ◽  
Author(s):  
Luca Scuderi ◽  
Sergio Davinelli ◽  
Clemente Maria Iodice ◽  
Silvia Bartollino ◽  
Giovanni Scapagnini ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Single Agent ◽  
Experimental Studies ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Physiological Processes ◽  
Age Related ◽  
Wide Range ◽  
Ocular Disorders ◽  
High Doses

Melatonin, an indoleamine secreted mainly by the pineal gland, is known to modulate a wide range of circadian functions. However, this neurohormone is also synthesized within the eye and acts directly on ocular structures to mediate a variety of physiological processes. This review is focused on the role and therapeutic potential of melatonin in ocular diseases. We summarize data indicating that melatonin may represent a powerful tool to counteract ocular dysfunctions such as uveitis, glaucoma, age-related macular degeneration, and diabetic retinopathy. A search strategy was conducted to identify studies in PubMed (January 1990 to September 2017). In particular, we included experimental studies, clinical trials, and reviews to provide suitable insights and elucidations regarding the action of melatonin on age-related ocular disorders. Literature data suggest that melatonin could potentially protect ocular tissues by decreasing the production of free radicals and pro-inflammatory mediators. Additionally, melatonin appears to be safe and well-tolerated, even at high doses, and no adverse/side effects were reported. Although this topic remains under intense investigation, we can conclude that melatonin, as a single agent or in combination with other drugs, is an attractive pharmacological candidate for age-related ocular diseases.

scholarly journals Microbiota and Ocular Diseases

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Xue ◽  
Jing Jing Li ◽  
Yanli Zou ◽  
Bin Zou ◽  
Lai Wei
Keyword(s):  
Therapeutic Potential ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Commensal Microbiota ◽  
Age Related ◽  
Organ Systems ◽  
Ocular Disorders ◽  
Ophthalmic Diseases ◽  
And Function ◽  
Generation Sequencing

Recent advances have identified significant associations between the composition and function of the gut microbiota and various disorders in organ systems other than the digestive tract. Utilizing next-generation sequencing and multiomics approaches, the microbial community that possibly impacts ocular disease has been identified. This review provides an overview of the literature on approaches to microbiota analysis and the roles of commensal microbes in ophthalmic diseases, including autoimmune uveitis, age-related macular degeneration, glaucoma, and other ocular disorders. In addition, this review discusses the hypothesis of the “gut-eye axis” and evaluates the therapeutic potential of targeting commensal microbiota to alleviate ocular inflammation.

Cell-based therapy for ocular disorders: A promising frontier

2021 ◽  
Vol 16 ◽  
Author(s):  
Milad Ahani-Nahayati ◽  
Vahid Niazi ◽  
Alireza Moradi ◽  
Bahareh Pourjabbar ◽  
Reza Roozafzoon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wide Spectrum ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Ocular Tissue ◽  
Ocular Diseases ◽  
Cell Based Therapy ◽  
Age Related ◽  
Ocular Disorders

: As the ocular disorders causing long-term blindness or optical abnormalities of the ocular tissue affect the quality of life of patients to a large extent, awareness of their corresponding pathogenesis and the earlier detection and treatment need more consideration. Though current therapeutics result in desirable outcomes, they do not offer an inclusive solution for development of visual impairment to blindness. Accordingly, stem cells, because of their particular competencies, have gained extensive attention for application in regenerative medicine of ocular diseases. In the last decades, a wide spectrum of stem cells surrounding mesenchymal stem/stromal cells (MSC), neural stem cells (NSCs), and embryonic/induced pluripotent stem cells (ESCs/iPSCs) accompanied by Müller glia, ciliary epithelia-derived stem cells, and retinal pigment epithelial (RPE) stem cells have been widely investigated to report their safety and efficacy in preclinical models and also human subjects. In this regard, in the first interventions, RPE cell suspensions were successfully utilized to ameliorate visual defects of the patients suffering from age-related macular degeneration (AMD) after subretinal transplantation. Herein, we will explain the pathogenesis of ocular diseases and highlight the novel discoveries and recent findings in the context of stem cell-based therapies in these disorders, focusing on the in vivo reports published during the last decade.

scholarly journals Ankle-brachial index and ocular diseases in a Russian population

Eye ◽  
2021 ◽  
Author(s):  
Mukharram M. Bikbov ◽  
Timur R. Gilmanshin ◽  
Rinat M. Zainullin ◽  
Ellina M. Rakhimova ◽  
Iuliia A. Rusakova ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Open Angle Glaucoma ◽  
Subclinical Atherosclerosis ◽  
Ankle Brachial Index ◽  
Age Related Macular Degeneration ◽  
Angle Closure ◽  
Glaucomatous Optic Neuropathy ◽  
Ocular Diseases ◽  
Age Related ◽  
Ocular Disorders

Abstract Background To assess potential associations between the ankle-brachial blood pressure index (ABI) and ocular disorders. Methods In the population-based cross-sectional Russian Ural Eye and Medical Study including 5,899 (80.5%) out of 7328 eligible participants aged 40+ years, the participants underwent a series of ocular and medical examinations including measurement of ABI. Results Blood pressure measurements of both arms and ankles were available for 3187 (54.0%) individuals. The mean ABI was 1.26 ± 0.19 (median:1.20; range: 0.61, 2.20). In multivariate analysis, a higher ABI was associated with younger age (P < 0.001; non-standardized regression coefficient B: −0.001; 95% confidence interval (CI): −0.002, −0.001), female sex (P < 0.001; B: 0.03; 95% CI: 0.02, 0.04), lower body mass index (P < 0.001; B: −0.004; 95% CI: −0.006, −0.003), lower waist-to-hip ratio (P = 0.01; B: −0.10; 95% CI: −0.17, −0.02), lower glucose serum concentration (P = 0.008; B: −0.005; 95% CI: −0.009, −0.001), lower prevalence of arterial hypertension (P < 0.001; B: −0.14; 95% CI: −0.16, −0.12), higher mean systolic blood pressure (P < 0.001; B: 0.003; 95% CI: 0.002, 0.003), and higher prevalence of any alcohol consumption (P < 0.001; B: 0.03; 95% CI: 0.02, 0.04). In that multivariate model, prevalence of glaucoma (P = 0.67) as a whole, open-angle glaucoma (P = 0.86) and angle-closure glaucoma (P = 0.54), stage of glaucomatous optic neuropathy (P = 0.57), prevalence of age-related macular degeneration (P = 0.88), prevalence and stage of diabetic retinopathy (P = 0.30, and P = 0.29, respectively), nuclear cataract (P = 0.32, and P = 0.41, resp.), cortical cataract (P = 0.33, and P = 0.92, resp.), subcapsular cataract (P = 0.74 and P = 0.60, resp.), and pseudoexfoliation (P = 0.44 and P = 0.47, resp.), intraocular pressure (P = 0.52), axial length (P = 0.20), and peripapillary retinal nerve fibre layer thickness (P = 0.55) were not significantly associated with the ABI. Conclusions In this ethnically mixed population from Russia, none of the major ocular diseases was associated with ABI suggesting that subclinical atherosclerosis is not markedly associated with the aetiology of these ocular disorders.

Oxidative Stress, Ocular Disease and Diabetes Retinopathy

2019 ◽  
Vol 24 (40) ◽  
pp. 4726-4741 ◽  
Author(s):  
Orathai Tangvarasittichai ◽  
Surapon Tangvarasittichai
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Death ◽  
Protein Modification ◽  
Morphological Changes ◽  
Corneal Dystrophy ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Retinal Light Damage ◽  
Age Related

Background: Oxidative stress is caused by free radicals or oxidant productions, including lipid peroxidation, protein modification, DNA damage and apoptosis or cell death and results in cellular degeneration and neurodegeneration from damage to macromolecules. Results: Accumulation of the DNA damage (8HOdG) products and the end products of LPO (including aldehyde, diene, triene conjugates and Schiff’s bases) were noted in the research studies. Significantly higher levels of these products in comparison with the controls were observed. Oxidative stress induced changes to ocular cells and tissues. Typical changes include ECM accumulation, cell dysfunction, cell death, advanced senescence, disarrangement or rearrangement of the cytoskeleton and released inflammatory cytokines. It is involved in ocular diseases, including keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, cataract, age-related macular degeneration, primary open-angle glaucoma, retinal light damage, and retinopathy of prematurity. These ocular diseases are the cause of irreversible blindness worldwide. Conclusions: Oxidative stress, inflammation and autophagy are implicated in biochemical and morphological changes in these ocular tissues. The development of therapy is a major target for the management care of these ocular diseases.

scholarly journals Clinical Perspectives and Trends: Microperimetry as a trial endpoint in retinal disease

2021 ◽  
Author(s):  
Yesa Yang ◽  
Hannah Dunbar
Keyword(s):  
Clinical Trial ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Gene Therapies ◽  
Age Related ◽  
Wide Range ◽  
Trial Endpoints ◽  
Visual Acuity Loss ◽  
Psychophysical Test ◽  
Trial Endpoint

Endpoint development trials are underway across the spectrum of retinal disease. New validated endpoints are urgently required for the assessment of emerging gene therapies and in preparation for the arrival of novel therapeutics targeting early stages of common sight-threatening conditions such as age-related macular degeneration. Visual function measures are likely to be key candidates in this search. Over the last two decades, microperimetry has been used extensively to characterize functional vision in a wide range of retinal conditions, detecting subtle defects in retinal sensitivity that precede visual acuity loss and tracking disease progression over relatively short periods. Given these appealing features, microperimetry has already been adopted as an endpoint in interventional studies, including multicenter trials, on a modest scale. A review of its use to date shows a concurrent lack of consensus in test strategy and a wealth of innovative disease and treatment-specific metrics which may show promise as clinical trial endpoints. There are practical issues to consider, but these have not held back its popularity and it remains a widely used psychophysical test in research. Endpoint development trials will undoubtedly be key in understanding the validity of microperimetry as a clinical trial endpoint, but existing signs are promising.

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.

Pegaptanib Sodium in the Treatment of Neovascular Age-Related Macular Degeneration

2010 ◽  
Vol 2 ◽  
pp. CMT.S2393
Author(s):  
Giuseppe Querques
Keyword(s):  
Macular Degeneration ◽  
Macular Edema ◽  
Single Agent ◽  
Age Related Macular Degeneration ◽  
Ocular Neovascularization ◽  
Pegaptanib Sodium ◽  
Anti Vegf ◽  
Age Related ◽  
Favorable Safety ◽  
Endothelial Growth Factor

Pegaptanib sodium is a polyethylene-glycolated, 28-nucleotide RNA aptamer that binds selectively to vascular endothelial growth factor (VEGF)165 but not smaller isoforms. Preclinical studies identified VEGF165 as an especially potent promoter of ocular neovascularization and inflammation. Following the pivotal clinical trials demonstrating the efficacy of intravitreal pegaptanib in treating all angiographic subtypes of neovascular age-related macular degeneration (NV-AMD), pegaptanib became the first anti-VEGF therapy to receive regulatory approval for this condition. In view of the importance of VEGF in a variety of tissues, including the cardiovascular system and the retina, concerns have been raised as to the risks that might accompany VEGF inhibition. It is thus of particular note that pegaptanib has proved to have a favorable safety record in treating NV-AMD, with no ocular or systemic safety signals having emerged over more than 4 years of clinical studies. Accordingly, in addition to its use as a single agent, pegaptanib has demonstrated promise in combinatorial regimens that employ nonselective anti-VEGF agents as an initial treatment followed by maintenance therapy with pegaptanib. Pegaptanib has also shown encouraging preliminary results in the treatment of diabetic macular edema, proliferative diabetic retinopathy, and macular edema secondary to retinal venous occlusive conditions.

Sign in / Sign up

Export Citation Format

Share Document