MIND4-17 protects retinal pigment epithelium cells and retinal ganglion cells from UV

// Chaopeng Li 1, * , Kang Yan 2, * , Wenqi Wang 1 , Qing Bai 1 , Changming Dai 1 , Xiaofeng Li 1 and Darui Huang 1 1 Department of Ophthalmology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China 2 Department of Ultrasound, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China * These authors share co-first authorship Correspondence to: Changming Dai, email: daicmnjmu@163.com Keywords: UV radiation, Nrf2, MIND4-17, retinal pigment epithelium cells, retinal ganglion cells Received: August 18, 2017 Accepted: September 03, 2017 Published: September 21, 2017 ABSTRACT Nrf2 activation would efficiently protect retinal cells from UV radiation (UVR). Recent studies have developed a Nrf2-targeting thiazole-containing compound MIND4-17, which activates Nrf2 through blocking its association with Keap1. In the current study, we demonstrated that pretreatment with MIND4-17 efficiently protected retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs) from UVR. UVR-induced apoptosis in the retinal cells was also largely attenuated by MIND4-17 pretreatment. MIND4-17 presumably separated Nrf2 from Keap1, allowing its stabilization and accumulation in retinal cells, which then translocated to cell nuclei and promoted transcription of ARE-dependent anti-oxidant genes, including HO1 , NQO1 and GCLM . Significantly, shRNA-mediated knockdown of Nrf2 almost completely abolished MIND4-17-induced cytoprotection against UVR. Further studies showed that MIND4-17 largely ameliorated UVR-induced ROS production, lipid peroxidation and DNA damages in RPEs and RGCs. Together, MIND4-17 protects retinal cells from UVR by activating Nrf2 signaling.