Altered DNA Methylation Profile Of 8-Oxoguanine DNA Glycosylase 1 In Lens Tissue From Age-Related Cataract Patients

Purpose To observe the altered expression of OGG1, 8-oxoguanine glycosylase1, a base excision repair enzyme for repairing oxidative DNA damage, in lens cortex from age-related cataract(ARC) patients and to examine the potential contribution of DNA methylation of CpG island in OGG1 to ARC pathogenesis.Methods A clinical case-control study was conducted in the department of ophthalmology from March 2013 to October 2013 in the Affiliated Hospital of Nantong University. Fifteen lens samples(7 males, 8 females, opacification of lenses=C4) with opacification of lenses were collected from ARC patients with no other ocular diseases according to the Lens Opacities Classification System III.Fifteen transparent control lens samples were obtained during vitrectomy. OGG1 expression in lens cortex was analyzed by RT-PCR and western blot. Using immuno- fluorescence, we determined the localization and the proportion of positive cells of OGG1. Bisulfite-sequencing PCR(BSP) was performed to evaluate methylation status of OGG1.Results The mRNA and protein levels of OGG1 were significantly reduced in the lens cortex of ARC group(t=4.39, P<0.01; t=7.95, P<0.01).Immunofluorescence showed that the proportion of OGG1-positive cells decreased significantly in ARC group(t=5.3, P<0.01). The CpG island in first exon of OGG1 displayed hypermethylation(t=11.64, P <0.01).Conclusions Hypermethylation of the CpG island of OGG1 in lens cortex of ARC is linked to the reduced OGG1 expression, which could result in susceptibility to oxidative stress and ARC.