Oxidative Damage Is a Potential Cause of Cone Cell Death in Retinitis Pigmentosa

Abstract

Abstract: : Purpose: Retinitis pigmentosa (RP) is a prevalent cause of blindness caused by a large number of different mutations in many different genes. The mutations result in rod photoreceptor cell death, but it is unknown why cones die. This study was designed to test the hypothesis that cones die from hyperoxia–induced damage in patients with RP. Methods: Indirect immunofluorescent staining was done for four biomarkers of oxidative damage a transgenic pig model of RP in which Pro347Leu mutated rhodopsin is expressed in rod photoreceptors. Results: The presence of acrolein– and 4–hydroxynonenal–adducts on proteins is a specific indicator that lipid peroxidation has occurred, and there was strong immunofluorescent staining for both in cone inner segments of 10 month–old transgenic pigs in which almost all rods had died, compared to faint staining in 10 month–old control pig retinas. In 22 month–old transgenic pigs in which all rods and many cones had died, staining was strong in cone axons and some cell bodies as well as inner segments indicating progression in oxidative damage between 10 and 22 months. There was also progressive increased staining for nitrotyrosine and 8–OH–deoxyguanosine, biomarkers for oxidative damage to proteins and DNA, respectively. Conclusions: These data support the hypothesis that death of rods results in decreased oxygen consumption and hyperoxia in the outer retina resulting in gradual cone cell death from oxidative damage.

Keywords: oxidation/oxidative or free radical damage • retinitis • immunohistochemistry