Modifications in stromal extracellular matrix of aged corneas can be induced by ultraviolet A irradiation.

Abstract

With age, structural and functional changes can be observed in human cornea. Some studies have shown a loss of corneal transparency and an increase in turbidity associated with aging. These changes are caused by modifications in the composition and arrangement of extracellular matrix in the corneal stroma. In human skin, it is well documented that exposure to solar radiation, and mainly to the UVA wavelengths, leads to phenotypes of photoaging characterized by alteration in extracellular matrix of the dermis. Although the cornea is also exposed to solar radiation, the extracellular matrix modifications observed in aging corneas have been mainly attributed to chronological aging and not to solar exposure. To ascertain the real implication of UVA exposure in extracellular matrix changes observed with age in human cornea, we have developed a model of photoaging by chronically exposing corneal stroma keratocytes with a precise UVA irradiation protocol. Using this model, we have analyzed UVA-induced transcriptomic and proteomic changes in corneal stroma. Our results show that cumulative UVA exposure causes changes in extracellular matrix that are found in corneal stromas of aged individuals, suggesting that solar exposure catalyzes corneal aging. Indeed, we observe a downregulation of collagen and proteoglycan gene expression and a reduction in proteoglycan production and secretion in response to cumulative UVA exposure. This study provides the first evidence that chronic ocular exposure to sunlight affects extracellular matrix composition and thus plays a role in corneal changes observed with age.