Nmnat1 as a Neuroprotective Agent in Murine Glaucoma

The purpose of this study is to evaluate the ability of overexpression of Nmnat1 to slow axonal degeneration in two mouse models of optic neuropathy.

Grantee institution at the time of this grant: Washington University

Glaucoma is the second leading cause of blindness worldwide and is characterized by degeneration of retinal ganglion cells (RGCs), whose axons make up the optic nerve. It is generally accepted that degeneration of the RGC axons precedes programmed death of the cell bodies themselves. Recent tissue culture experiments have shown that increased expression of the Nmnat1 gene can slow the rate of axonal degeneration in the face of axonal injury. The purpose of this study is to evaluate the ability of overexpression of Nmnat1 to slow axonal degeneration in two mouse models of optic neuropathy. In the first model, a short period of very high eye pressure will be used to cause RGC damage over 1-2 weeks. The second model uses application of laser to the eye to moderately and stably raise eye pressure, closely simulating glaucoma. A virus vector containing the Nmnat1 gene will be injected into eyes from each of these models, and the RGCs will be evaluated both morphologically and functionally to determine if Nmnat1 can protect the RGCs against damage. This study will efficiently assess the potential of Nmnat1 to serve as an effective anti-glaucoma agent.