Faculty Collaboration Database

Photoreceptor Survival Is Regulated by GSTO1-1 in the Degenerating Retina. Invest Ophthalmol Vis Sci 2018 Sep 04;59(11):4362-4374

Date

09/08/2018

Pubmed ID

30193308

DOI

10.1167/iovs.18-24627

Scopus ID

2-s2.0-85053083915 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

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 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.

Author List

Fernando N, Wooff Y, Aggio-Bruce R, Chu-Tan JA, Jiao H, Dietrich C, Rutar M, Rooke M, Menon D, Eells JT, Valter K, Board PG, Provis J, Natoli R

Author

Janis Eells PhD Professor in the Biomedical Sciences department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Animals
Biomarkers
Blotting, Western
Carrier Proteins
Cell Survival
Complement C3
Cytokines
Disease Models, Animal
Electroretinography
Female
Genetic Markers
Glutathione Transferase
Immunohistochemistry
Male
Mice
Mice, Inbred C57BL
Oxidative Stress
Photoreceptor Cells
Real-Time Polymerase Chain Reaction
Retina
Retinal Degeneration