| First Author | Schultz R | Year | 2016 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 57 |
| Issue | 10 | Pages | 4115-24 |
| PubMed ID | 27537261 | Mgi Jnum | J:254617 |
| Mgi Id | MGI:6112437 | Doi | 10.1167/iovs.16-19260 |
| Citation | Schultz R, et al. (2016) Increased Frataxin Levels Protect Retinal Ganglion Cells After Acute Ischemia/Reperfusion in the Mouse Retina In Vivo. Invest Ophthalmol Vis Sci 57(10):4115-24 |
| abstractText | PURPOSE: The mitochondrial protein frataxin (FXN) is highly expressed in metabolically active tissues and has been shown to improve cell survival in response to oxidative stress after ischemia. Retinal ischemia/hypoxia is a complication of ocular diseases such as diabetic retinopathy and glaucoma. There are no effective therapeutic approaches currently available. This study was performed to evaluate the neuroprotective effects of FXN after acute retinal ischemia/reperfusion in vivo. METHODS: Retinal ischemia/reperfusion was induced in adult wild-type and FXN-overexpressing mice by transient elevation of intraocular pressure (IOP) for 45 minutes. Expression of FXN was evaluated by quantitative (q)RT-PCR and Western blot analysis between 6 and 48 hours after ischemia. Retinal ganglion cell (RGC) survival was determined with immunofluorescent staining and fluorescence microscopy 14 days after lesion. Expression of hypoxia-inducible factors Hif-1alpha and Hif-2alpha and of oxidative stress markers heme oxygenase-1 (Hmox1), glutathione peroxidase 1 (Gpx1), superoxidase dismutase 1 and 2 (Sod1, Sod2), and catalase was evaluated by qRT-PCR. RESULTS: Endogenous FXN levels were upregulated for up to 24 hours after retinal ischemia in vivo. Retinal ganglion cell survival was significantly improved in FXN-overexpressing mice 14 days after ischemia. Expression of antioxidative enzymes Gpx1, Sod2, and catalase was significantly increased in FXN-overexpressing mice after lesion. CONCLUSIONS: Retinal FXN levels are increased in response to ischemia. Furthermore, elevated FXN levels had a clear neuroprotective effect as shown by increased ganglion cell survival after acute retinal ischemia/reperfusion. Frataxin''s neuroprotective effect was associated with an upregulation of antioxidative enzymes. The data suggest that FXN induces neuroprotection by decreasing oxidative stress. |
