Investigating the Role of PGC-1 Beta in Neovascular AMD
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.
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
About the Researcher
Dr. Magali Saint-Geniez received her PhD degree from the University of Toulouse, France, where she trained in vascular research at the ISERM laboratory. Dr. Saint-Geniez joined the Schepens Eye Research Institute of Massachusetts Eye and Ear Infirmary in 2002 to complete her post-doctoral training in the laboratory of Dr. Patricia D’Amore, where she studied the role of vascular endothelial growth factor in ocular development and maintenance of retinal homeostasis. She is now an assistant scientist at the Schepens Eye Research Institute and assistant professor in the Department of Ophthalmology, Harvard Medical School. Her current research program focuses on characterizing novel molecular pathways involved in common retinal degenerative diseases, such as AMD. In particular, she is investigating the underlying pathogenic roles of metabolic dysfunction and oxidative damage in photoreceptors and RPE, and is evaluating the therapeutic benefits of novel metabolic regulators using multidisciplinary approaches, including bioengineering, molecular and metabolic biology of novel in vitro and in vivo disease models.
Finding a cure for retinal degenerative disease is much more than an academic goal, it is a very personal one. Spending my summers with my dearly loved aunt on a farm in the south of France, I watched her going blind from macular degeneration. Each year she was becoming less independent and losing her ability to recognize members of the family. I am more determined than ever to use my research to restore sight, hopefully allowing my aunt to one day see my little boy’s face. With the generous support of the BrightFocus Foundation and its donors, my laboratory and collaborators will be able to better understand how macular degeneration progress to the most severe and blinding stage of the disease, with the hope of discovering new and potentially very powerful therapies.
First published on: September 25, 2018
Last modified on: June 10, 2020