Generation of Retinal Ganglion Cells by Reprogramming

Glaucoma is a disease that causes vision loss and blindness in millions of people. This proposal aims to improve existing procedures and establish new ones to generate retinal ganglion cells, the cells affected in glaucoma, in a petri dish. The cells thus produced will be used to study the reasons causing glaucoma, to screen for drugs to treat it, and to develop new therapeutic strategies.

The goal of this proposal is to improve existing and to establish new procedures for efficient generation of retinal ganglion cells (RGCs), the major cell type affected in one of the most common eye diseases, glaucoma. Our experimental design is based on our recent finding that two genes are essential and sufficient for RGC differentiation during development. We will develop procedures in which these two genes, along with others if necessary, are activated in induced pluripotent stem cells  or fibroblasts (ie, cells that were themselves grown from adult human cell samples) so that these cells can be directed to differentiate into RGCs. If successful, the RGCs thus generated can be used to model the disease in vitro, to screen for drugs that can prevent their death, and to develop treatment of the disease by cell replacement.