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

Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4362-4374. doi: 10.1167/iovs.18-24627.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Biomarkers
  • Carrier Proteins
  • Complement C3
  • Cytokines
  • Genetic Markers
  • Gsto1 protein, mouse
  • Glutathione Transferase