Studying mechanism of oxidative stress induced changes in Retinal Pigment Epithelium (RPE) that controls retinal degeneration. Age-related macular degeneration (AMD) causes vision loss among many older individuals, and the retinal pigment epithelium (RPE) is thought to be a critical site of injury. Vision loss in AMD occurs due to photoreceptor degeneration and/or choroidal neovascularization. Geographic atrophy (GA), the advanced form of dry AMD, is characterized by the breakdown of RPE, choriocapillaris, and photoreceptors, especially in the macula. Lack of clear understanding of the molecular mechanisms of GA hinders the development of therapy. For lifelong maintenance of photoreceptors, RPE cells play an essential role in phagocytosis and degradation of tips shed from photoreceptor outer segments (POS). Photoreceptors and RPE cells are susceptible to injury from mitochondrial oxidative stress. The central goal of the project is to understand how photoreceptor degeneration occurs in GA. We hypothesize that oxidative stress impairs phagocytosis and lysosome function and ultimately activates inflammatory processes in RPE that stimulate geographic atrophy. We are testing our hypothesis in RPE cell culture and in a new mouse model of age-dependent RPE atrophy.
Developing and testing potential translationaltherapy (Gene/Drug/Nano) for treating retinal degenerative and vascular diseases. The abnormal growth of blood vessels in the eye may originate from cornea, retina and choroid. New blood vessels originating from the choroid layer is a major implication in wet age-related macular degeneration (wet-AMD). New blood vessels originating from retina are the clinical phenotype for diabetic retinopathy (DR) and retinopathy of prematurity (ROP). In either case, local secretion of VEGF induces uncontrolled neovascularization that ultimately causes irreversible damage to the retina causing a loss of vision that cannot be restored. Retinal degeneration is associated with loss of photoreceptor cells and RPE that is caused due to prolonged oxidative stress. We are testing different potential AAV mediated therapeutic genes that can be used to protect retinal cells and RPE. We are also testing different FDA approved drugs and new drugs that have the capacity to prevent retinal degeneration and abnormal neovascularization. Students from MSPN graduate program focus on developing and testing different nanoparticle based approach that carry genes and drugs to protect the retina from oxidative and inflammatory insult. We are using different model systems to test novel translational therapy that will be useful to treat retinal degenerative and vascular diseases.