DNA damage in lens epithelium of cataract patientsin vivoandex vivo

Abstract

ABSTRACT.Purpose: DNA damage has been described in the human cataractous lens epithelium, and oxidative stress generated by UV radiation and endogenous metabolic processes has been suggested to play a significant role in the pathogenesis of cataract. In this study, the aim was to explore the quality and relative quantity of DNA damage in lens epithelium of cataract patients in vivo and after incubation in a cell culture system. Methods: Capsulotomy specimens were analysed, before and after 1 week of ex vivo cultivation, using the comet assay to measure DNA strand breaks, oxidized purine and pyrimidine bases and UV-induced cyclobutane pyrimidine dimers. Results: DNA strand breaks were barely detectable, oxidized pyrimidines and pyrimidine dimers were present at low levels, whereas there was a relatively high level of oxidized purines, which further increased after cultivation. Conclusion: The observed levels of oxidized purines in cataractous lens epithelium may support a theory consistent with light damage and oxidative stress as mediators of molecular damage to the human lens epithelium. Damage commonly associated with UV-B irradiation was relatively low. The levels of oxidized purines increased further in a commonly used culture system. This is of interest considering the importance and versatility of ex vivo systems in studies exploring the pathogenesis of cataract.

DNA Damage in Lens Epithelial Cells and Peripheral Lymphocytes from Age-Related Cataract Patients

“…Our results confirmed a significantly higher level of DNA damage in LECs and lymphocytes in ARC patients than in control subjects. Our results supported the hypothesis that ARC was an oxidative disorder and prominent DNA damage in lens and whole system could lead to ARC, which was consistent with previous studies [3,5,17,20]. As far as we know, this is the first study to measure DNA damage by comet assay in LECs and peripheral lymphocytes of cataract patients.…”

“…The antioxidative defenses are lower and oxidative stress products are higher in the lenses and aqueous humor of cataract patients [4,18]. A few studies found DNA damage in both cultured human LECs and fresh LECs from senile cataract patients [3,19,20,21]. …”

“…Kleiman and Spector [21] first reported DNA damage of LECs in human cataract by using the alkaline comet assay. Recently, there have been two studies to further confirm DNA damage in cataractous LECs by comet assay [3,20]. …”

Cataract frequency and subtypes involved in workers assessed for their solar radiation exposure: a systematic review

“…The two main mechanisms for the induction of cataracts by ocular UV light exposure are oxidative stress and its resultant inflammation (Varma et al 2011;Øsnes-Ringen et al 2013) and phototoxidation that may involve photosensitizers (Roberts 2011). These may be endogenous, as metabolites of inert tryptophan enzymatically modified with age (Balasubramanian 2000) or UV absorbing advanced glycation end products (Ortwerth et al 1997), or exogenous photosensitizers, for example phototoxic drugs (Roberts 2002).…”

Polymorphisms of DNA Repair Genes XPD (Lys751Gln) and XRCC1 (Arg399Gln), and The Risk of Age-Related Cataract: A Meta-Analysis

“…This damage may contribute to cataractogenesis. [6][7][8] The physiological role of DNA repair is to protect the genome against damage caused by environmental factors, and therefore is critically important for the maintenance of a clear lens. 9 DNA repair depends on several enzymes that are coded for by DNA repair genes.…”