Is There Excess Oxidative Stress and Damage in Eyes of Patients with Retinitis Pigmentosa?

Abstract

Retinitis pigmentosa (RP) is a group of diseases in which a mutation in one of the large variety of genes causes death of rod photoreceptors. After rods die, cone photoreceptors gradually die resulting in constriction of visual fields and eventual blindness in many patients. Studies in animal models of RP have demonstrated that oxidative damage is a major contributor to cone cell death. In this study, we extended those findings to patients with RP, because compared to control patients, those with RP showed significant reduction in the reduced to oxidized glutathione (GSH/GSSG) ratio in aqueous humor and a significant increase in aqueous protein carbonyl content. In contrast, there was no significant decrease in the serum GSH/GSSG ratio or increase in carbonyl content of serum proteins. These data indicate that patients with RP have ocular oxidative stress and damage in the absence of manifestations of systemic oxidative stress and/or damage indicating that demonstrations of oxidative damage-induced cone cell death in animal models of RP may translate to human RP. These observations lead to the hypothesis that potent antioxidants will promote cone survival and function in patients with RP and that the aqueous GSH/GSSG ratio and carbonyl content on proteins may provide useful biomarkers. Antioxid. Redox Signal. 23, 643-648.

FIG. 1.

Comparison between retinitis pigmentosa (RP) patients and controls in carbonyl content of proteins in aqueous and serum. Aqueous samples from nine RP and nine control patients were assayed for protein carbonyl content and total protein. Control patients had macular pucker or macular hole, but no other eye diseases. Serum samples from eight RP and seven control patients were also assayed. Each bar represents the mean (±standard deviation) carbonyl content per mg total protein and statistical comparisons were made with Student's unpaired t-test. NS, not significant.

FIG. 2.

Comparison between RP and control patients in malondialdehyde (MDA) level in aqueous and serum. Aqueous samples from seven RP and six control patients and serum samples from eight RP and seven controls were assayed for MDA. The bars represent the mean (±standard deviation). Statistical comparisons by Student's unpaired t-test showed no statistically significant differences.

FIG. 3.

Comparison between RP patients and controls in reduced glutathione to oxidized glutathione ratio (GSH/GSSG) in aqueous and serum. Aqueous samples from seven RP and six control patients and serum samples from nine RP and seven controls were assayed for GSH/GSSG ratio. The bars represent the mean (±standard deviation) GSH/GSSH ratio and statistical comparisons were made by Student's unpaired t-test.

FIG. 4.

Comparison between RP and control patients in superoxide dismutase 3 (SOD3) level in serum. Serum samples were from eight RP and eight control patients were assayed for SOD3. Each bar represents the mean (±standard deviation) SOD3 per ml of sample. Statistical comparison by Student's unpaired t-test showed no significant difference.