Abstract
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.
Highlights
Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the developed world, affecting 11 million people in the U.S and 170 million people world-wide [1,2]
Several groups have found that an intestinal dysbiosis occurs in AMD patients, and that certain dietary changes can cause AMD-like phenotypes due to changes in the microbiota
Additional work proving the implication that AREDS and dietary changes may be beneficial in preventing the progression of AMD through their action on the intestinal microbiota, and will require experimentation in both animal models and longitudinal data collection in patients
Summary
Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the developed world, affecting 11 million people in the U.S and 170 million people world-wide [1,2]. Due to the increasing aging population, the number of AMD-affected individuals is expected to double by the year 2050 [2]. An intersection of genetic and environmental factors likely contribute to AMD pathogenesis. These factors include disruptions in lipid, carotenoid, and inflammatory pathways induced by diet, smoking, and certain gene variants [3,4]. It has been shown that spouses of subjects who develop AMD were more likely to develop the disease themselves, suggesting that shared lifestyle habits, and potentially, shared microbiota, may increase risk [7]
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