Stress Signaling in the Survival and Repair of RGCs
Disease processes in glaucoma harm the connections that allow your eye to send visual information to your brain. This harm stimulates natural repair processes that ultimately fail and even end up further contributing to the loss of vision. Our proposal aims to understand how these repair processes switch from providing hope for recovery to causing greater damage. Appropriate stimulation of these processes may allow for restoration of vision.
My laboratory seeks ways to stimulate the innate repair potential of the retinal neurons that are most affected in glaucoma. These neurons initiate repair programs in response to the injuries they receive during the disease process. In glaucoma, however, these programs actually end up doing more harm them good, even resulting in neuronal death and accelerating the permanent loss of vision. Our first goal is to understand how this response goes from being a potential source of recovery to a major contributor to blindness. Secondly, we aim to unleash the potential of these repair programs, carefully stimulating them in combination with other interventions that are showing early promise for restoring vision. Our approach to achieving these goals centers on the engineering of new genetic tools that allow us to fine-tune the injury response. We can stimulate mild, moderate, or severe responses and change their pattern and timing to determine the precise level of activity that is most beneficial without triggering adverse effects. In the near term, the understanding we gain may reveal the sweet spot, sometimes called a “therapeutic window,” in which drugs that can tame the neuronal injury response might help to prevent the death of retinal neurons in glaucoma. Over the longer term, we seek to coax the innate repair programs of these surviving neurons to help re-establish communication between the eye and the brain for the restoration of vision.