Reactive Oxygen Species Promote Localized DNA Damage in Glaucoma Iris Tissues of Elderly Patients Vulnerable to Diabetic Injury

Abstract

Purpose: : Glaucoma is typically an insidious-onset disease with serious visual consequences that has been positively linked to diabetes mellitus (DM). Glaucoma is more often present in the elderly. An important prognostic factor of glaucoma might be oxidative stress resulting from glucose toxic effect and diabetes-associated vascular complications.

Methods: : Fifty-five patients and control subjects aged 71.0 ± 10.1 yr were enrolled in this study. Iris tissue samples from DM type 2 patients, primary open-angle glaucoma positive and negative DM patients, and healthy subjects were examined by alkaline comet assay. We measured the DNA damage levels of strand breaks (SB), oxidized purines as glicosylo-formamido-glicosyalse (Fpg) sites, and oxidized pirmidines as endonuclease III (Nth) sites.

Results: : It was found that the level of oxidative damage in iris tissue was statistically higher in DM and glaucoma patients than in controls (Fpg = 38.0% and 34.7% vs. 15.4%; Nth = 43.3% and 39.0% vs. 23.3%; P < 0.001). It was also found that SBs were higher in diabetic patients than in controls (43% vs. 34%; P < 0.001). Interestingly, in comparison to healthy controls, we found extremely elevated levels of oxidized purines and pirmidines in glaucomatous patients with DM (Fpg = 55.7% vs. 15.4%; Nth = 61.8% vs. 23.3%; P < 0.001).

Conclusions: : Our observations suggest that generation of a reactive oxygen species might promote localized DNA damage in iris tissues vulnerable to diabetic injury what in turn might reflect the general pro/anti-oxidant status in the eye.

Keywords: diabetes • genetics • oxidation/oxidative or free radical damage