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Photoreceptor Survival Is Regulated by GSTO1-1 in the Degenerating Retina

Fernando, Nilisha; Wooff, Yvette; Aggio-Bruce, Riemke; Chu-Tan, Joshua; Jiao, Haihan; Dietrich, Catherine; Rutar, Matthew; Rooke, Melissa; Menon, Deepthi; Eells, Janis T; Valter, Krisztina; Board, Philip; Provis, Jan; Natoli, Riccardo

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PURPOSE. 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...[Show more]

dc.contributor.authorFernando, Nilisha
dc.contributor.authorWooff, Yvette
dc.contributor.authorAggio-Bruce, Riemke
dc.contributor.authorChu-Tan, Joshua
dc.contributor.authorJiao, Haihan
dc.contributor.authorDietrich, Catherine
dc.contributor.authorRutar, Matthew
dc.contributor.authorRooke, Melissa
dc.contributor.authorMenon, Deepthi
dc.contributor.authorEells, Janis T
dc.contributor.authorValter, Krisztina
dc.contributor.authorBoard, Philip
dc.contributor.authorProvis, Jan
dc.contributor.authorNatoli, Riccardo
dc.date.accessioned2019-04-15T10:59:37Z
dc.date.available2019-04-15T10:59:37Z
dc.identifier.issn0146-0404
dc.identifier.urihttp://hdl.handle.net/1885/159662
dc.description.abstractPURPOSE. 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.
dc.format.mimetypeapplication/pdf
dc.language.isoen_AU
dc.publisherAssociation for Research in Vision and Ophthalmology
dc.rights2018 The Authors
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceInvestigative Ophthalmology and Visual Science
dc.titlePhotoreceptor Survival Is Regulated by GSTO1-1 in the Degenerating Retina
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume59
dc.date.issued2018
local.identifier.absfor111303 - Vision Science
local.identifier.ariespublicationu4485658xPUB120
local.type.statusPublished Version
local.contributor.affiliationFernando, Nilisha, College of Health and Medicine, ANU
local.contributor.affiliationWooff, Yvette, College of Health and Medicine, ANU
local.contributor.affiliationAggio-Bruce, Riemke, College of Health and Medicine, ANU
local.contributor.affiliationChu-Tan, Joshua, College of Health and Medicine, ANU
local.contributor.affiliationJiao, Haihan, College of Health and Medicine, ANU
local.contributor.affiliationDietrich, Catherine, College of Health and Medicine, ANU
local.contributor.affiliationRutar, Matthew, College of Health and Medicine, ANU
local.contributor.affiliationRooke, Melissa, College of Health and Medicine, ANU
local.contributor.affiliationMenon, Deepthi, College of Health and Medicine, ANU
local.contributor.affiliationEells, Janis T, University of Wisconsin-Milwaukee
local.contributor.affiliationValter, Krisztina, College of Health and Medicine, ANU
local.contributor.affiliationBoard, Philip, College of Health and Medicine, ANU
local.contributor.affiliationProvis, Jan, College of Health and Medicine, ANU
local.contributor.affiliationNatoli, Riccardo, College of Health and Medicine, ANU
local.bibliographicCitation.issue11
local.identifier.doi10.1167/iovs.18-24627
local.identifier.absseo920107 - Hearing, Vision, Speech and Their Disorders
dc.date.updated2019-03-12T07:28:21Z
local.identifier.scopusID2-s2.0-85053083915
dcterms.accessRightsOpen Access
dc.rights.licenseThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
CollectionsANU Research Publications

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