Fernando, NilishaWooff, YvetteAggio-Bruce, RiemkeChu-Tan, JoshuaJiao, HaihanDietrich, CatherineRutar, MatthewRooke, MelissaMenon, DeepthiEells, Janis TValter, KrisztinaBoard, PhilipProvis, JanNatoli, Riccardo2019-04-152019-04-150146-0404http://hdl.handle.net/1885/159662PURPOSE. Glutathione-S-transferase omega 1-1 (GSTO1-1) is a cytosolic glutathione transferase enzyme, involved in glutathionylation, toll-like receptor signaling, and calcium channel regulation. GSTO1-1 dysregulation has been implicated in oxidative stress and inflammation, and contributes to the pathogenesis of several diseases and neurological disorders; however, its role in retinal degenerations is unknown. The aim of this study was to investigate the role of GSTO1-1 in modulating oxidative stress and consequent inflammation in the normal and degenerating retina. METHODS. The role of GSTO1-1 in retinal degenerations was explored by using Gsto1/ mice in a model of retinal degeneration. The expression and localization of GSTO1-1 were investigated with immunohistochemistry and Western blot. Changes in the expression of inflammatory (Ccl2, Il-1β, and C3) and oxidative stress (Nox1, Sod2, Gpx3, Hmox1, Nrf2, and Nqo1) genes were investigated via quantitative real-time polymerase chain reaction. Retinal function in Gsto1/ mice was investigated by using electroretinography. RESULTS. GSTO1-1 was localized to the inner segment of cone photoreceptors in the retina. Gsto1/ photo-oxidative damage (PD) mice had decreased photoreceptor cell death as well as decreased expression of inflammatory (Ccl2, Il-1β, and C3) markers and oxidative stress marker Nqo1. Further, retinal function in the Gsto1/ PD mice was increased as compared to wild-type PD mice. CONCLUSIONS. These results indicate that GSTO1-1 is required for inflammatory-mediated photoreceptor death in retinal degenerations. Targeting GSTO1-1 may be a useful strategy to reduce oxidative stress and inflammation and ameliorate photoreceptor loss, slowing the progression of retinal degenerations.application/pdfen-AU2018 The Authorshttps://creativecommons.org/licenses/by-nc-nd/4.0/201810.1167/iovs.18-246272019-03-12This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License