Down-regulation of Fra-2 alleviates light-induced retina damage by inhibiting the PARP-1/AIF pathway.

Visible light has been previously demonstrated to induce retina damage and retinal ganglion cell (RGC) death through the mitochondrial pathway. The Fra-2 gene was detected as a transcriptional regulator, but whether it is involved in light-induced retina damage remains unclear. In this study, we investigated the effect of Fra-2 on a light-induced mouse retinal damage model and in vitro RGC-5 cells. Tissues lysed and ripped were observed in the inner nuclear layer (INL) and the ganglion cell layer (GCL) of the retina after mice were exposed to light for 12 h. Light exposure significantly increased the expression of Fra-2 and PARP-1 in a time-dependent manner. Light exposure or the up-regulation of Fra-2 significantly increased the apoptosis and decreased the proliferation of RGC-5 cells. At the same time, the down-regulation of Fra-2 or NU1025 exposure significantly inhibited light-induced RGC-5 cell apoptosis and induced the proliferation of light-induced RGC-5 cells. Light exposure or up-regulation of Fra-2 significantly increased the expression of PARP-1 and nuclear AP-1, but the down-regulation of Fra-2 or NU1025 exposure significantly attenuated those protein expressions. Those results suggest that Fra-2 is involved in light induced retinal damage and causes cell death by the activation of the PARP-1/AIF signaling pathway. Down-regulation of Fra-2 might alleviate light-induced retinal damage via inhibiting PARP-1-independent AIF release.