Astroglial Contributions to Glaucoma

Project Summary

Glaucoma is a leading cause of blindness in the world and affects an estimate 3 million Americans. In most cases, glaucoma is caused by elevated intraocular pressure that damages the optic nerve and eventually leads to death of retinal ganglion cells (cells that extend nerve fibers to form the optic nerve). Current therapy for glaucoma is directed at lowering intraocular pressures, but very often, it fails to prevent the progressive neuron and vision loss associated with the disease. Therefore, finding ways that protect the optic nerve and c from injury are crucial to the development of more efficacious treatment for glaucoma. Retinal astroglial cells are supporting cells of the retina. Accumulating evidence suggests that when these supporting cells respond to nerve injury, they induce detrimental effect on the nerve and retinal ganglion cells, thus, may contribute critically to the development and progression of the disease. In the present application, we hypothesize that responses of these supporting cells are directly responsible for glaucoma-induced optic nerve damage and retinal ganglion cell death by producing neurotoxic agents, triggering inflammation, and generating an inhospitable environment. The objective of this research plan will define the functional roles of these supporting cells in optic nerve and retinal ganglion cell damage in glaucoma and eventually, design drugs that prevent neuronal damage and vision loss by targeting to the function of these cells. We have proposed three Specific Aims: * Aim I will investigate the functional roles of these supporting cells in optic nerve and retinal ganglion cell degeneration in a glaucoma mouse model as well as test the effect of a potential chemical that can eliminate the detrimental effects of the supporting cells. * Aim II will further prove the concept by defining the roles of these supporting cells using a genetically engineered mouse models. * Aim III will take advantage of the new technology of cDNA microarray to determine the molecular basis underlying the detrimental effects of the supporting cells after nerve injury. Results derived from this study will provide important information for developing new therapeutic strategies to treat glaucoma and other brain and optic nerve damage.