Role of Nrf2 in Protecting RGC in Glaucoma

Oxidative stress and inflammatory processes are thought to play important roles in the development and progression of glaucoma. The research proposed in this application will determine the role of NF-E2-related factor 2 (Nrf2, a critical cellular stress-responsive protein) in preventing ganglion cell death. Dr. Xu and colleagues will also evaluate the potential of Nrf2 activation drugs in preventing cell death and vision loss in a mouse model of glaucoma.

The proposed research will determine the potential of targeting NF-E2-related factor 2 (Nrf2) for the treatment of vision loss in glaucoma.

Vision loss in glaucoma results from progressive retinal ganglion cell (RGC) death. Oxidative stress and inflammatory processes play important roles in the development and progression of glaucoma. Nrf2 is considered to control one of the most important cellular pathways to protect against oxidative stress, and it also has an important role as a negative regulator of inflammation, essentially dialing-down the out-of-control inflammation associated with many diseases. Dr. Xu and colleagues will use cell culture studies and a mouse model of glaucoma to determine whether regulating Nrf2 will help promote RGC survival. The first aim of the study is to determine whether the activation or inactivation of Nrf2 affects RGC survival when exposed to oxidative stress. The second aim of the study is to test the potential of using a drug to activate Nrf2 to protect RGCs in a mouse model of glaucoma. The proposed research could help to develop a new treatment strategy for glaucoma. In addition, this work will further the understanding of the role of oxidative stress and inflammation in the development and progression of glaucoma.