Investigating the Role of PGC-1 Beta in Neovascular AMD

Magali Saint-Geniez, PhD The Schepens Eye Research Institute, Harvard Medical School


Vision loss in AMD is caused by the dysfunction and loss of the retinal pigment epithelium (RPE), a pigmented layer of cells which support the photosensitive photoreceptors. RPE health and protective functions depend on their metabolism, the highly regulated process controlling energy production and by-products detoxification. Here we will study a novel pathogenic mechanism responsible for impaired RPE metabolism and progression to the advanced neovascular form of AMD.

Project Details

Central vision loss has a profound impact on the quality of life of affected patients. In age-related macular degeneration (AMD), such loss is attributed to the defect and/or loss of the retinal pigment epithelium (RPE), a thin layer of cells that nourishes, recycles and detoxifies the photoreceptors (the light sensitive cells of the retina). In about 10 percent of AMD patients, the disease progresses to a proliferative form (neovascular AMD - nAMD) where pathological and leaky vessels invade the retina, leading to rapid and severe central vision loss. While significant efforts have been invested in the basic and clinical characterization of nAMD pathogenesis, the origins of RPE dysfunction leading to pathological blood vessel growth remain unclear. To function, RPE cells rely on tightly regulated energy production and by-products detoxification, but in AMD, this metabolic process is impaired, leading to oxidative damage and cellular dysfunction.  Recently our lab has identified a novel protein linking RPE metabolism to the pathological blood vessel formation observed in advanced AMD.  Our current project will further investigate how dysregulation of this protein in the context of AMD alters RPE energy production and promotes progression to nAMD. Results from this study will help us to better understand the underlying pathogenic mechanisms of AMD and open up new avenues for efficient and specific therapeutic strategies