Reduced inspired oxygen decreases retinal superoxide radicals and promotes cone function and survival in a model of retinitis pigmentosa

Retinitis pigmentosa (RP) is caused by many different mutations that promote the degeneration of rod photoreceptors and have no direct effect on cones. After the majority of rods have died cone photoreceptors begin to slowly degenerate. Oxidative damage contributes to cone cell death and it has been hypothesized that tissue hyperoxia due to reduced oxygen consumption from the loss of rods is what initiates oxidative stress. Herein, we demonstrate in animal models of RP that reduction of retinal hyperoxia by reducing inspired oxygen to continuous breathing of 11% O2 reduced the generation of superoxide radicals in the retina and preserved cone structure and function. These data indicate that retinal hyperoxia is the initiating event that promotes oxidative damage, loss of cone function, and cone degeneration in the RP retina. [Display omitted] •In RP, after rods die from a mutation, cones are exposed to hyperoxia.•Hyperoxia causes activation of NADPH oxidase, promoting oxidative damage in cones.•Oxidative damage causes loss of function and eventual death of cones.•Reduced inspired oxygen in mice with RP reduces tissue hyperoxia.•Reduced Hyperoxia reduces oxidative damage and promotes cone survival and function.