Superoxide dismutase 1 protects retinal cells from oxidative damage

Aling Dong, Jikui Shen, Melissa Krause, Hideo Akiyama, Sean F. Hackett, Hong Lai, Peter A. Campochiaro

Research output: Contribution to journalArticlepeer-review

Abstract

Bolstering the endogenous oxidative damage defense system is a good strategy for development of treatments to combat neurodegenerative diseases in which oxidative damage plays a role. A first step in such treatment development is to determine the role of various components of the defense system in cells that degenerate. In this study, we sought to determine the role of superoxide dismutase 1 (SOD1) in two models of oxidative damage-induced retinal degeneration. In one model, paraquat is injected into the vitreous cavity and then enters retinal cells and generates reactive oxygen species (ROS) that cause progressive retinal damage. Assessment of retinal function with serial electroretinograms (ERGs) showed that sod1-/- mice were much more sensitive than sod1+/+ mice to the damaging effects of paraquat, while sod1+/- mice showed intermediate sensitivity. Compared to sod1+/+ mice, sod1-/- mice showed greater paraquat-induced oxidative damage and apoptosis. In the second model, mice were exposed to hyperoxia for several weeks, and sod-/- mice showed significantly greater reductions in ERG amplitudes than sod1+/+ mice. In both of these models, transgenic mice carrying a sod1 transgene driven by a β-actm promoter showed less oxidative stress-induced reduction in ERG amplitudes. These data demonstrate that SOD1 protects retinal cells against paraquat- and hyperoxia-induced oxidative damage and suggest that overexpression of SOD1 should be considered as one component of ocular gene therapy to prevent oxidative damage-induced retinal degeneration.

Original languageEnglish (US)
Pages (from-to)516-526
Number of pages11
JournalJournal of Cellular Physiology
Volume208
Issue number3
DOIs
StatePublished - Sep 1 2006

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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