Effects of nerve damage on supporting cells in glaucoma

Dong Chen, MD, PhD
The Schepens Eye Research Institute (Boston, MA)
Year Awarded:
2007
Grant Duration:
April 1, 2007 to March 31, 2009
Disease:
Glaucoma
Award Amount:
$90,000
Grant Reference ID:
G2007058
Award Type:
Standard
Award Region:
US Northeastern

Astroglial Contributions to Glaucoma

Summary

In the present application, we hypothesize that responses retinal astroglial 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.

Details


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.

Publications

Takeda, M., Takamiya, A., Jiao, J.W., Cho, K.S., Trevino, S.G., Matsuda, T., and Chen, D.F. (2008) alpha-Aminoadipate induces progenitor cell properties of Muller glia in adult mice. Invest Ophthalmol Vis Sci. 49(3):1142-50.  

Jiao J and Chen DF. Induction of neurogenesis in non-conventional neurogenic regions of the adult CNS by niche astrocyte-produced signals. (2008) Stem Cells; 26(5):1221-1230.  

Tucker B, Klassen H, Yang L, Chen DF, Young MJ. Elevated MMP Expression in the MRL Mouse Retina Creates a Permissive Environment for Retinal Regeneration. (2008) Invest Ophthalmol Vis Sci. 49(4):1686-1695.  

Cho K-S and Chen DF. Promoting Optic Nerve Regeneration in Adult Mice with Pharmaceutical Approach. (2008) Neurochem Res. 33(10):2126-2133.  

Verardo M, Lewis GP, Takeda M, Linberg KA, Byun J, Luna G, Wilhelmsson U, Pekny M, Chen DF, Fisher SK. Abnormal Reactivity of Mueller Cells After Retinal Detachment in Mice Deficient in GFAP and Vimentin. (2008) Invest Ophthalmol Vis Sci. 49(8):3659-65.  

Chen H, Wei X, Cho K-S, Chen G, Sappington R, Calkins D, and Chen DF. Optic neuropathy in a bead-induced mouse model of elevated intraocular pressure. Invest Ophthalmol Vis Sci. 2008; submitted. [PMID:nd][link not available] Wei X, Zhang Y, Wang X, and Chen DF. Neuroprotective effect of neuroglobin in glaucoma. Under preparation [PMID: nd][link not available]
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