Grant: Operating Grant

Glaucoma is the leading cause of irreversible blindness worldwide. At present, there is no cure for glaucoma and current therapies are inadequate. Loss of vision in glaucoma results from the irreversible death of retinal ganglion cells, the neurons that send visual information from the retina to the brain. The current proposal will focus on novel observations made by our team to provide an in-depth characterization of key pathways leading to retinal ganglion cell degeneration. Specifically, we will test the hypothesis that early deficits in retinal ganglion cell dendrites initiate a cascade of cellular damage that ultimately results in dysfunction and death. The scientific foundation of this project lies on our recent observation that substantial dendritic abnormalities occur early in an experimental mouse glaucoma model, and that this response is caused by a loss of the 'mammalian target of rapamycin (mTOR)' activity, a key intracellular regulator of cell growth and protein synthesis. This research program will create knowledge concerning the molecular and cellular mechanisms of RGC dendritic damage, and it will validate novel targets for the development of therapeutic strategies to protect vision in glaucoma.