Role of CHOP and ER Stress in RGC Degeneration

These experiments seek to determine if inhibition of the stress induced response can reduce or prevent the loss of retinal ganglion cells. If successful, this work could help provide the basis for the development of new strategies for the diagnosis and treatment of glaucoma.

Glaucoma is a major cause of vision loss. It is the second most common cause of blindness worldwide. In glaucoma, decreased vision is caused by the injury and death of retinal ganglion cells (RGCs), the cells that transmit visual information from the eye to the brain. All current forms of glaucoma treatment (drugs, laser treatment, and surgery) act by lowering the pressure within the eye. Although pressure lowering can be helpful, RGC loss can continue even after pressure reduction. Greater understanding of the molecular mechanisms underlying retinal ganglion cell (RGC) loss will likely make possible the development of more effective diagnostic and treatment strategies. In the work proposed in this application we will explore the molecular mechanisms that actually induce the death of RGCs. In preliminary studies we have shown that a particular pathway, called the stress induced response, is activated in animal models of glaucoma. We propose to study this pathway in more detail, and determine if inhibition of the stress induced response can reduce or prevent the loss of RGCs.