Oxidative deoxyribonucleic acid damage in the eyes of glaucoma patients

Abstract

Some investigators have hypothesized that oxidative damage may be involved as a molecular mechanism of glaucoma. Levels of 8-hydroxy-2`-deoxyguanosine (8-OH-dG) were measured in the trabecular meshwork region from 42 patients with glaucoma and 45 age- and sex-matched controls. Genotypes of glutathione S-transferase isoenzymes (GTSM1 and GSTT1) were assessed by polymerase chain reaction in the same DNA samples. Levels of 8-OH-dG were significantly higher in glaucoma patients vs controls. Oxidative DNA damage in patients with glaucoma correlated significantly with intraocular pressure; in patients with primary open-angle glaucoma, it also correlated with visual field defects. GSTT1 was similar in the two groups, and had no effect on 8-OH-dG levels. Conversely, 8-OH-dG levels were significantly higher in GSTM1-null than in GSTM1-positive subjects. The GSTM1-null genotype was significantly more common in patients with primary open-angle glaucoma than in controls. Oxidative DNA damage is significantly increased in the trabecular meshwork of glaucoma patients. GSTM1 gene deletion, which has been associated with an increased risk of cancer at various sites and molecular lesions in atherosclerosis, predisposes to more severe oxidative DNA damage in glaucoma patients.—Hans E. Grossniklaus