Interplay Between Inflammation and Cell Metabolism in AMD

This project explores how metabolic function and mitochondrial health of the retinal pigment epithelium are impacted during the inflammatory response of AMD. Metabolic dysfunction is emerging as a key mechanism driving many age-related diseases, including AMD. This project explores how metabolic function and mitochondrial health of the retinal pigment epithelium are impacted during the inflammatory response of AMD. Drugs that target metabolic pathways and mitochondria will be evaluated for their efficacy in blocking the inflammatory response in the retinal pigment epithelial cells.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly, and with our aging population, the number of AMD cases is expected to increase to 288 million in 2040. Tumor necrosis factor alpha (TNFa) is a protein that mediates inflammatory processes and has been identified to play a role in AMD. Metabolic dysfunction is emerging as another mechanism in many age-related diseases including AMD. With age, our metabolic function declines and our mitochondria (responsible for generating energy) become dysfunctional. Little is known about the metabolic effects of TNFa in AMD. Thus, this proposal seeks to increase our understanding of the interplay between metabolism and inflammation in AMD. Sirtuin1 activators such as resveratrol (found in red wine) are drugs known to enhance metabolic function and suppress inflammation and their efficacy in blocking TNFa will be tested as a potential drug target for AMD.

Little is known about the interplay between inflammatory and metabolic dysfunction in the retinal pigment epithelium. By unravelling the precise mechanisms governing this interplay, we can find novel metabolic targets and test their efficacy in dampening the inflammatory response, thereby opening innovative therapeutic approaches to treat age-related macular degeneration.

Understanding the interplay of inflammation and metabolism in RPE will not only enhance our understanding of the pathogenesis of age-related macular degeneration (AMD) but also enable the identification of novel drug targets for treating AMD and restoring vision. The findings from this study will also enhance our foundational biological understanding of inflammation and metabolism and serve to inspire more studies investigating this relationship in other diseases with an inflammatory component.