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.
Highlights
Retinal degenerative diseases are characterized by progressive loss of retinal cells [1,2,3]
We demonstrated that pretreatment with MIND4-17 efficiently protected retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs) from UV radiation (UVR)
We aim to study the potential effect of this NF-E2-related factor 2 (Nrf2)-inducing compound on UV radiation (UVR)-induced retinal cell damages
Summary
Retinal degenerative diseases are characterized by progressive loss of retinal cells [1,2,3]. Intense recent studies have been focusing on exploring novel strategies to protect retinal cells from UVR/oxidative stresses [6,7,8,9]. As a transcription factor, activated Nrf binds to the antioxidant responsive elements (AREs). It dictates transcription and expression of multiple genes, including those of endogenous antioxidants, phase II detoxification enzymes, along with other cellular defensive proteins [10,11,12,13]. Studies have demonstrated that Nrf2-dependent antioxidant response is a pivotal protection system against oxidative insults in mammalian cells [7, 14,15,16]
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