Accumulation of Epigenetic Noise in the Aging Corneal Epithelium and Its Possible Mechanism

The cornea is the eye's "window" and plays an important role in vision. Aging has a substantial impact on corneal function by reducing the ability of corneal cells to protect the eye, refract light, and repair itself. In this study, we investigated DNA methylation patterns and the activity of the DNMT and TET families, which are responsible for shaping these patterns, in the aging corneal epithelium. To this end, we used corneal epithelial cell sheets detached from the corneas of 2- and 14-month-old mice to study gene expression, DNA methylation, and DNA hydroxymethylation. We detected significant changes in gene expression in aging corneal epithelial cells. Our data indicate that aging leads to significant changes in the methylation of individual cytosines and large DNA regions, which were similar to those shown for other aging tissues. We observed reduced expression of genes from the DNMT and TET families and reduced DNA hydroxymethylation levels in the corneal epithelium of 14-month-old mice compared to 2-month-old mice. These data indicate that the activity of TET enzymes is reduced in the corneal epithelium during aging. Thus, we found an accumulation of epigenetic noise in the aging corneal epithelium, manifested by increases and decreases in DNA methylation levels, which may be caused by decreased activity of TET enzymes. We propose that the observed age-related changes in the corneal epithelium reflect epigenetic changes occurring in the limbal epithelial stem cells.