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Peng Zhou, Yi Lu; Changes in the Pattern of DNA Methylation in Age-Related Cataract. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1266.
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Age-related cataract (ARC) is the leading cause of blindness among the elderly. DNA methylation, a major control program that modulates gene expression, is related to age-related disease. The purpose of this study was to identify possible differences in DNA methylation in the central epithelium of age-related cataractous human lenses and age-related controls.
Using 5-methyl-cytosine DNA immunoprecipitation followed by Illumina sequencing (MeDIP-seq), we investigated the DNA methylation profiles of 10 eyes with age-related nuclear cataracts and 10 age-matched controls. The MeDIP-seq results were validated by bisulfite sequencing, pyrosequencing, reverse-transcription PCR and Western blot.
We identified 101,278 cataract-associated differentially methylated regions (cDMRs). Analysis showed these cDMRs to be significantly enriched in the promoter of some genes that related to lens and suggests an association between aberrant DNA methylation of these genes and the pathogenesis of age-related cataract. Of those genes, αA-crystallin gene was selected because its chaperone-like activity is considered to be critical for the maintenance of eye lens transparency. The mRNA and protein levels of αA-crystallin were significantly reduced in the lens epithelia of age-related cataract cases versus controls, which corresponded to hypermethylation of the CpG island of αA-crystallin promoter. Treatment with zebularine, a DNA demethylating agent, was associated with restoration of αA-crystallin expression.
The evidence presented suggests that DNA methylation plays potential roles in age-related cataract formation. This study is useful for a deeper understanding of the pathogenesis of age-related cataract, and it can be used to identify novel opportunities for the prevention of and therapy for cataract.
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