Oxidation and age-related macular degeneration: insights from molecular biology

Author(s):  
Sam Khandhadia ◽  
Andrew Lotery

Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. It is a multifactorial disease, and current therapy predominantly limits damage only when it has already occurred. The macula is a source of high metabolic activity, and is therefore exposed to correspondingly high levels of reactive oxygen species (ROS). With age, the balance between production of ROS and local antioxidant levels is shifted, and damage ensues. Systemic ROS and antioxidant levels in AMD reflect these local processes. Genetic studies investigating mutations in antioxidant genes in AMD are inconclusive and further studies are indicated, especially to determine the role of mitochondria. Oral antioxidant supplements could be beneficial, and diet modification may help. Future treatments might either increase antioxidant capacity or reduce the production of ROS, using methods such as genetic manipulation. This article reviews the role of oxidative stress in AMD and the potential therapies that might have a role in preventing the blindness resulting from this disease.

2021 ◽  
Vol 13 ◽  
pp. 251584142110304
Author(s):  
Mousumi Banerjee ◽  
Rohan Chawla ◽  
Atul Kumar

Age-related macular degeneration (ARMD) is one of the prominent causes of central visual loss in the older age group in the urbanized, industrialized world. In recent years, many epidemiological studies and clinical trials have evaluated the role of antioxidants and micronutrients to prevent the progression of ARMD. In this article, we review some of these major studies. In addition, we review the absorption and bioavailability and possible undesirable effects of these nutrients after ingestion. The role of genotypes and inappropriate use of these supplements are also discussed. From all the above evidence, we conclude that it may not be prudent to prescribe these formulations without a proper assessment of the individual’s health and dietary status. The effectiveness of all the components in antioxidant formulations is controversial. Thus, these supplements should not be prescribed just for the purpose of providing patients some kind of therapy, which may give a false sense of mental satisfaction.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donita L. Garland ◽  
Eric A. Pierce ◽  
Rosario Fernandez-Godino

AbstractThe complement system plays a role in the formation of sub-retinal pigment epithelial (RPE) deposits in early stages of age-related macular degeneration (AMD). But the specific mechanisms that connect complement activation and deposit formation in AMD patients are unknown, which limits the development of efficient therapies to reduce or stop disease progression. We have previously demonstrated that C3 blockage prevents the formation of sub-RPE deposits in a mouse model of EFEMP1-associated macular degeneration. In this study, we have used double mutant Efemp1R345W/R345W:C5-/- mice to investigate the role of C5 in the formation of sub-RPE deposits in vivo and in vitro. The data revealed that the genetic ablation of C5 does not eliminate the formation of sub-RPE deposits. Contrarily, the absence of C5 in RPE cultures promotes complement dysregulation that results in increased activation of C3, which likely contributes to deposit formation even in the absence of EFEMP1-R345W mutant protein. The results also suggest that genetic ablation of C5 alters the extracellular matrix turnover through an effect on matrix metalloproteinases in RPE cell cultures. These results confirm that C3 rather than C5 could be an effective therapeutic target to treat early AMD.


2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke

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.


2016 ◽  
Vol 16 (5) ◽  
pp. 699-709 ◽  
Author(s):  
Muhammad Hassan ◽  
Rubbia Afridi ◽  
Mohammad Ali Sadiq ◽  
Mohamed Kamel Soliman ◽  
Aniruddha Agarwal ◽  
...  

2021 ◽  
Vol 10 (10) ◽  
pp. 2072
Author(s):  
Phoebe Lin ◽  
Scott M. McClintic ◽  
Urooba Nadeem ◽  
Dimitra Skondra

Blindness from age-related macular degeneration (AMD) is an escalating problem, yet AMD pathogenesis is incompletely understood and treatments are limited. The intestinal microbiota is highly influential in ocular and extraocular diseases with inflammatory components, such as AMD. This article reviews data supporting the role of the intestinal microbiota in AMD pathogenesis. Multiple groups have found an intestinal dysbiosis in advanced AMD. There is growing evidence that environmental factors associated with AMD progression potentially work through the intestinal microbiota. A high-fat diet in apo-E-/- mice exacerbated wet and dry AMD features, presumably through changes in the intestinal microbiome, though other independent mechanisms related to lipid metabolism are also likely at play. AREDS supplementation reversed some adverse intestinal microbial changes in AMD patients. Part of the mechanism of intestinal microbial effects on retinal disease progression is via microbiota-induced microglial activation. The microbiota are at the intersection of genetics and AMD. Higher genetic risk was associated with lower intestinal bacterial diversity in AMD. Microbiota-induced metabolite production and gene expression occur in pathways important in AMD pathogenesis. These studies suggest a crucial link between the intestinal microbiota and AMD pathogenesis, thus providing a novel potential therapeutic target. Thus, the need for large longitudinal studies in patients and germ-free or gnotobiotic animal models has never been more pressing.


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