| First Author | Nagar S | Year | 2017 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 58 |
| Issue | 9 | Pages | 3741-3749 |
| PubMed ID | 28738418 | Mgi Jnum | J:257604 |
| Mgi Id | MGI:6112357 | Doi | 10.1167/iovs.17-21767 |
| Citation | Nagar S, et al. (2017) Molecular Pathway to Protection From Age-Dependent Photoreceptor Degeneration in Mef2 Deficiency. Invest Ophthalmol Vis Sci 58(9):3741-3749 |
| abstractText | Purpose: Photoreceptor degeneration in the retina is a major cause of blindness in humans. Elucidating mechanisms of degenerative and neuroprotective pathways in photoreceptors should afford identification and development of therapeutic strategies. Methods: We used mouse genetic models and improved methods for retinal explant cultures. Retinas were enucleated from Mef2d+/+ and Mef2d-/- mice, stained for MEF2 proteins and outer nuclear layer thickness, and assayed for apoptotic cells. Chromatin immunoprecipitation (ChIP) assays revealed MEF2 binding, and RT-qPCR showed levels of transcription factors. We used AAV2 and electroporation to express genes in retinal explants and electroretinograms to assess photoreceptor functionality. Results: We identify a prosurvival MEF2D-PGC1alpha pathway that plays a neuroprotective role in photoreceptors. We demonstrate that Mef2d-/- mouse retinas manifest decreased expression of PGC1alpha and increased photoreceptor cell loss, resulting in the absence of light responses. Molecular repletion of PGC1alpha protects Mef2d-/- photoreceptors and preserves light responsivity. Conclusions: These results suggest that the MEF2-PGC1alpha cascade may represent a new therapeutic target for drugs designed to protect photoreceptors from developmental- and age-dependent loss. |
