Cell Autonomous Neuroprotection by the Mitochondrial Uncoupling Protein 2 in a Mouse Model of Glaucoma.

Glaucoma is a group of disorders associated with retinal ganglion cell (RGC) degeneration and death. There is a clear contribution of mitochondrial dysfunction and oxidative stress toward glaucomatous RGC death. Mitochondrial uncoupling protein 2 () is a well-known regulator of oxidative stress that increases cell survival in acute models of oxidative damage. The impact of on cell survival during sub-acute and chronic neurodegenerative conditions, however, is not yet clear. Herein, we test the hypothesis that increased expression will improve RGC survival in a mouse model of glaucoma. We show that increasing RGC but not glial expression in transgenic animals decreases glaucomatous RGC death, but also that the PPAR-γ agonist rosiglitazone (RSG), an endogenous transcriptional activator of , does not significantly alter RGC loss during glaucoma. Together, these data support a model whereby increased expression mediates neuroprotection during a long-term oxidative stressor, but that transcriptional activation alone is insufficient to elicit a neuroprotective effect, motivating further research in to the post-transcriptional regulation of .