Grant: CIHR Fellowship

Today, 80 million people worldwide suffer from glaucoma. This disease is the second leading cause of blindness in developed countries. Glaucoma results from an abnormal increase in pressure in the eye, which compresses the optic nerve and cuts the communication bridge between the eye and the brain. The retinal neurons that send their extension to the brain via the optic nerve, known as retinal ganglion cells (RGCs), die in this pathology. Unfortunately, these cells are unable to regenerate spontaneously in humans, and mammals in general. One hope of treatment lay in transplanting new RGCs into the retina to replace the dead cells. However, transplants are a risky therapy, particularly in terms of potential graft rejection. An alternative therapeutic approach is therefore required. To this end, we propose a cell reprogramming therapy that involves transforming support cells, known as glial cells, already present in the retina into new RGCs. In this way, the newly-formed cells will replace the RGCs lost due to pathology and cannot be rejected, since the glial cells used are already part of the retinal tissue. To achieve this, we plan to use a cocktail of genetic modifications by injecting viral vectors into the eyes of mice in a glaucoma model. First, we will study the mechanisms by which genetic modifications induce glial cell reprogramming. Next, we will characterize the identity of the newly-formed RGCs to verify that they correspond to the RGCs initially present in the retina. Finally, we will evaluate the ability of the new RGCs to re-project their extension into the optic nerve in a mouse model of glaucoma.