Exendin-4 protects retinal pigment epithelial cells against oxidative stress in vitro via PI3K/Akt-STAT3 activation

The glucagon-like peptide 1 (GLP-1) analogue Exendin-4 (Ex-4) could perform anti-oxidative effects against oxidative damage both in vitro and in vivo. However, little was known about the direct protection of Exendin-4 on RPE cells against oxidative stress and its underlying mechanism. The present study examined the protective effects of Exendin-4 on RPE cells against H2O2 treatment in vitro and retina I/R injury in vivo. The results indicated that Ex-4 exerted protective effects under H2O2 condition on RPE cells and attenuated the oxidative stress-induced damage, as evidenced by the results of cellular viability, cytotoxicity, apoptosis and western blotting. However, the protective effects of Ex-4 were mainly abrogated by p-Akt inhibitor or p-STAT3 inhibitor. In conclusion, the Ex-4 was able to protect RPE cells from H2O2 induced oxidative damage in vitro and attenuate retinal injury from I/R in vivo, which was closely related to PI3k/Akt and p-STAT3 signaling.