Nuclear and Mitochondrial DNA of Age-Related Cataract Patients Are Susceptible to Oxidative Damage

Abstract

ABSTRACTPurpose: Reactive oxygen species caused by oxidative stress are considered as an important risk factor in the pathogenesis of age-related cataract (ARC). In addition, it has been shown that DNA damage has a potential role in the pathogenesis of cataract. In this study, background DNA damage, oxidative stress-induced DNA damage, and repair of nuclear and mitochondrial DNA of peripheral blood mononuclear cells (PBMCs) of ARC patients were investigated.Methods: The study population included 30 age-matched and sex-matched controls with 30 ARC patients aged 50 years and older. Acute oxidative stress was induced by 200 µM H2O2. The DNA damage was determined using gene-specific quantitative PCR-based assay in DNA extracted from PBMCs, both at basal condition and after (0, 6, and 20 h) acute oxidative stress.Results: Background level of mitochondrial DNA frequency was higher in cataract patients. The present study revealed that, for the first time, both nDNA and mtDNA of cataract patients were sensitive to the oxidative stress in comparison with healthy individuals. It was found that oxidative DNA damage in PBMCs was almost all repaired within 20 h. Also, time-dependent repair of nDNA and mtDNA damage was not different between cataract patients and healthy individuals.Conclusions: Our findings clearly demonstrate that both nDNA and mtDNA in cataract patients are susceptible to oxidative DNA damage and background level of mitochondrial DNA damage was higher. Also, these results suggest that oxidative DNA damage accumulation (especially mtDNA damage) can play a crucial role in pathogenesis of cataract.