SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling

// Yi-qing Gong 1, 2, * , Wei Huang 1, * , Ke-ran Li 1, * , Yuan-yuan Liu 3, * , Guo-fan Cao 1 , Cong Cao 3 , Qin Jiang 1 1 The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China 2 Ophthalmology Department, Zhenjiang First People's Hospital, Zhenjiang, China 3 Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China * These authors contributed equally to this work Correspondence to: Qin Jiang, email: Jqin710@vip.sina.com Guo-fan Cao, email: 1548397844@qq.com Cong Cao, email: caocong@suda.edu.cn Keywords: retinal pigment epithelium, UV, SC79, Akt, Nrf2 signaling Received: June 13, 2016 Accepted: July 20, 2016 Published: August 09, 2016 ABSTRACT Excessive Ultra-violet (UV) radiation causes oxidative damages and apoptosis in retinal pigment epithelium (RPE) cells. Here we tested the potential activity of SC79, a novel small molecule activator of Akt, against the process. We showed that SC79 activated Akt in primary and established (ARPE-19 line) RPE cells. It protected RPE cells from UV damages possibly via inhibiting cell apoptosis. 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. Reversely, Nrf2 shRNA knockdown or S40T mutation attenuated SC79-induced anti-UV activity. For the in vivo studies, we showed that intravitreal injection of SC79 significantly protected mouse retina from light damages. Based on these results, we suggest that SC79 protects RPE cells from UV damages possibly via activating Akt-Nrf2 signaling axis.