Glaucoma is a leading cause of irreversible vision loss worldwide. Glaucoma is an optic neuropathy with age and increased intraocular pressure (IOP) as the two main risk factors for development of vision loss. An inbred mouse strain (DBA2/J) has been identified which spontaneously develops increased IOP and optic nerve damage as the mice age, similar to the chronic, progressive course of human glaucomatous disease. In this career training grant application, we will use the DBA2/J glaucoma model to identify molecular and cellular mechanisms of glaucoma. We will test the hypothesis that the retinal ganglion cell-specific transcription factor brn-3b is specifically down-regulated by raised intraocular pressure that induces RGC death. The demonstration that brn-3b plays a functionally important role in glaucoma will provide a molecular target for neuroprotective strategies with which to treat human glaucoma.
Specific Aim A will correlate the cellular, molecular, and functional changes in the retina as glaucoma progresses in the DBA2/J mouse model of glaucoma.
This aim will determine the structure-function correlation between the brn-3b and retinal ganglion cells with visual function in glaucoma.
Specific Aim B will determine if down-regulation of the retinal ganglion cell-specific transcription factor brn-3b is functionally associated with raised intraocular pressure and the development of glaucoma in in vivo models.
Specific Aim C will determine if brn-3b is neuroprotective for retinal ganglion cells by over expressing brn-3b in RGC and determining if brn-3b is anti-apoptotic in RGC cell culture and in vivo systems. This grant's specific aims will characterize a popular animal model of glaucoma, lead to important discoveries in our understanding of glaucoma, and develop the career of the principal investigator as a clinician scientist. ? ?
| Munguba, Gustavo C; Galeb, Sanja; Liu, Yuan et al. (2014) Nerve fiber layer thinning lags retinal ganglion cell density following crush axonopathy. Invest Ophthalmol Vis Sci 55:6505-13 |
| Aref, Ahmad A; Sayyad, Fouad E; Ayres, Bernadete et al. (2013) Acute bilateral angle closure glaucoma induced by methazolamide. Clin Ophthalmol 7:279-82 |
| Munguba, Gustavo C; Geisert, Eldon E; Williams, Robert W et al. (2013) Effects of glaucoma on Chrna6 expression in the retina. Curr Eye Res 38:150-7 |
| Goel, Manik; Sienkiewicz, Adam E; Picciani, Renata et al. (2012) Cochlin, intraocular pressure regulation and mechanosensing. PLoS One 7:e34309 |
| Chong, Gabriel T; Lee, Richard K (2012) Glaucoma versus red disease: imaging and glaucoma diagnosis. Curr Opin Ophthalmol 23:79-88 |
| Rachitskaya, Aleksandra V; Lee, Richard K; Dubovy, Sander R et al. (2012) Combined central retinal vein and central retinal artery occlusions and neovascular glaucoma associated with interferon treatment. Eur J Ophthalmol 22:284-7 |
| Shane, Thomas S; Shi, Wei; Schiffman, Joyce C et al. (2012) Used glasses versus ready-made spectacles for the treatment of refractive error. Ophthalmic Surg Lasers Imaging 43:235-40 |
| Olmos, Lisa C; Lee, Richard K (2011) Medical and surgical treatment of neovascular glaucoma. Int Ophthalmol Clin 51:27-36 |
| Goel, Manik; Sienkiewicz, Adam E; Picciani, Renata et al. (2011) Cochlin induced TREK-1 co-expression and annexin A2 secretion: role in trabecular meshwork cell elongation and motility. PLoS One 6:e23070 |
| Munguba, Gustavo C; Camp, Andrew S; Risco, Miguel et al. (2011) Vesicular glutamate transporter 3 in age-dependent optic neuropathy. Mol Vis 17:413-9 |
Showing the most recent 10 out of 19 publications
