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Nilisha Fernando, Yvette Wooff, Riemke Aggio-Bruce, Joshua A. Chu-Tan, Haihan Jiao, Catherine Dietrich, Matt Rutar, Melissa Rooke, Deepthi Menon, Janis T. Eells, Krisztina Valter, Philip G. Board, Jan Provis, Riccardo Natoli; Photoreceptor Survival Is Regulated by GSTO1-1 in the Degenerating Retina. Invest. Ophthalmol. Vis. Sci. 2018;59(11):4362-4374. doi: https://doi.org/10.1167/iovs.18-24627.
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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.
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.
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.
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.
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