Treating age-related macular degeneration through enhanced lysosomal degradation of A2E - Ghezal Beliakoff

Video Overview

Age Related Macular Degeneration (AMD) is the leading cause of visual loss among people 65 years and older. This disease manifests into two distinct forms, wet and dry. The pathogenesis for both forms is poorly understood and numerous hypothetical models have been studied to better understand their mechanism. The dry form of AMD involves atrophy of the retinal pigment epithelium (RPE) by the accumulation of bisretinoid lipofuscin within lysosomes as the cells phagocytose the outer membranes of the photoreceptors. A major fluorescent component of RPE lipofuscin is a compound known as pyridinum bisretinoid (A2E). We have been able to degrade A2E by exogenous enzyme delivery to cultured human RPE cells and cell free systems. We have discovered an enzyme (SENS20) that, in the presence of its co-substrate, has the ability to degrade A2E in a dose-dependent manner without damaging RPE cells. This dose-dependency is evident in vitro and in cell culture assays. Our studies show evidence for SENS20’s positive enzymatic activity towards synthetic A2E cultured with human RPE cells and its ability for potential treatment of dry AMD.