Superoxide dismutase 1 protects retinal cells from oxidative damage.
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 sod1 -/- 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 beta-actin 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.
Dong
Aling
A
Department of Ophthalmology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA.
Shen
Jikui
J
Krause
Melissa
M
Akiyama
Hideo
H
Hackett
Sean F
SF
Lai
Hong
H
Campochiaro
Peter A
PA
D000818:Animals; D002467:Cell Nucleus / Q000648:ultrastructure; D004596:Electroretinography; D017353:Gene Deletion; D018496:Hyperoxia; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D010269:Paraquat / Q000633:toxicity; D012160:Retina / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics*; D000072105:Superoxide Dismutase-1
C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D010269:Paraquat