Discovery of New Methods to Regenerate Cone Photoreceptors

Project Summary

The goal of this study is to develop a method to form new cone photoreceptors to replace those lost during (due to) age-related macular degeneration (AMD). More specifically, we will use a directed molecular approach to identify genes that are able to transform non-cones into cones. This study is innovative in that it leverages both the recent advances in our understanding of how cone cells develop, and a genetic mouse model with cone cells that glow green to increase the probability of success in the identification of our genes of interest. In addition, cutting edge technology that examines the expression of many genes at once in single cells will be used to make robust conclusions about the effectiveness of our cone-forming protocol. At the completion of our study, we anticipate that we will have both increased our understanding of how cone cells form and identified new therapeutic avenues to replace cone cells lost in the course of AMD. In our first aim, we will test whether non-cone retinal cells are able to be transformed into cones upon expression of specific genes in these cells. We will use a mouse model with fluorescently labeled cone cells in order to detect the presence and precise number of these cells. In our second aim, we will do a detailed analysis of these transformed cells to determine how closely they resemble cones. This will be important to determine if the expression of multiple genes is required to form fully functional cone photoreceptors that can be used to replace those lost during AMD.