SC79 Protects Retinal Pigment Epithelium Cells From UV Radiation Via Activating Akt-Nrf2 Signaling

Purpose:Excessive Ultra-violet(UV)radiation causes oxidative damages and apoptosis in retinal pigment epithelium(RPE)cells.We tested the potential activity of SC79,a novel small molecule activator of Akt,against the process.The signaling mechanisms were analyzed.Methods:In order to test the protective effect of SC79 on UV-induced RPE cells,MTT assays and trypan blue staining assays were used to detect cell viability;Annexin V/propidium iodide staining,Histone DNA apoptosis enzyme-linked immunosorbent assay,caspase9 activity and mitochondrial depolarization were used to detect RPE cells apoptosis.We detect the Akt levels in the RPE cells activated by SC79 by Western blot.The Akt signaling mechanism was analyzed by MK-2206,the inhibitors of Akt,and Aktl shRNA;the Nrf2 signaling mechanism was analyzed by using qRT-PCR to detect the influences of HO-1,NQO1,Nrf2 in RPE cells,as well as to detect the protective effects on SC79 of Nrf2 shRNA and mutated dominant negative Nrf2(DN,S40T).At last,retinal ERG was used to test mouse retina from light damages in the mouse withintravitreal injection of SC79.Results:SC79 protected RPE cells from UV damages.SC79 activated Akt in RPE cells.Akt inhibition,via an Akt specific inhibitor(MK-2206)or Akt1 shRNA silence,almost abolished SC79-induced RPE cytoprotection.Further studies showed that SC79 activated Akt-dependent NF-E2-related factor 2(Nrf2)signaling and inhibited UV-induced oxidative stress in RPE cells.For the in vivo studies,we showed that intravitreal injection of SC79 significantly protected mouse retina from light damages.Conclusion:SC79 protects RPE cells from UV damages possibly via activating Akt-Nrf2 signaling axis.