Abstract
Age-related macular degeneration (AMD) is a common cause of visual impairment in the elderly. There are very limited therapeutic options for AMD with the predominant therapies targeting vascular endothelial growth factor (VEGF) in the retina of patients afflicted with wet AMD. Hence, it is important to remind readers, especially those interested in AMD, about current studies that may help to develop novel therapies for other stages of AMD. This study, therefore, provides a comprehensive review of studies on human specimens as well as rodent models of the disease, to identify and analyze the molecular mechanisms behind AMD development and progression. The evaluation of this information highlights the central role that oxidative damage in the retina plays in contributing to major pathways, including inflammation and angiogenesis, found in the AMD phenotype. Following on the debate of oxidative stress as the earliest injury in the AMD pathogenesis, we demonstrated how the targeting of oxidative stress-associated pathways, such as autophagy and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, might be the futuristic direction to explore in the search of an effective treatment for AMD, as the dysregulation of these mechanisms is crucial to oxidative injury in the retina. In addition, animal models of AMD have been discussed in great detail, with their strengths and pitfalls included, to assist inform in the selection of suitable models for investigating any of the molecular mechanisms.
Highlights
Age-related macular degeneration (AMD) is a neurodegenerative disease that affects the central retina of an aging eye, resulting in a progressive loss of vision and a common cause of visual impairment and disability in the aging population [1]
Rodent models of retinal degeneration provide valuable evidence for the mechanisms involved in AMD and help elucidate how these mechanisms may be interrelated with each other (Figure 2)
The role of oxidative stress is implicated in the inducement of inflammation in the Y402H polymorphism, which is considered the most important genetic risk of AMD
Summary
Age-related macular degeneration (AMD) is a neurodegenerative disease that affects the central retina of an aging eye, resulting in a progressive loss of vision and a common cause of visual impairment and disability in the aging population [1]. Retinal changes observed in the AMD eyes are varied and include (1) loss of the RPE and photoreceptor layer, (2) accumulation of lipids and protein deposits beneath the RPE or in the BrM, and (3) choriocapillaris dropout, CNV, and disciform scarring [8, 9]. In addition to these is inflammation response through the recruitment of macrophages and microglia, and complement activation [10, 11]. They observed that in wet AMD or choroidal neovascularization (CNV), choriocapillaris loss preceded RPE atrophy, implicating the choriocapillaris as the focus of injury in wet AMD, which in turn could induce hypoxia in the adjacent RPE, upregulating vascular endothelial growth factor (VEGF), and promoting CNV [9]
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