Senolytic drugs ameliorate the corneal epithelial barrier function through the elimination of senescent cells.

Abstract

Purpose : Corneal epithelial permeability increases with aging. Cellular senescence is one of the hallmarks of aging and we previously reported that the senescent corneal epithelial cells accumulate with aging. Here, we investigated the role of senescent human corneal epithelial cells (CECs) and therapeutic potential of senolytics against the senescence-associated phenotype.

Methods : We used human primary CECs obtained from donor corneas. Human CECs were exposed to irradiation (IR) at 10 Gy and were cultured for 10 days to undergo senescent. The epithelial barrier function of senescent CECs was measured with a volt-ohm meter. ABT263, a Bcl-2 inhibitor as a senolytic drug was used, and cell viability of senescent CECs and the transepithelial electrical resistance (TEER) was examined as a barrier function.

Results : Senescent CECs displayed a lower barrier level compared to non-senescent CECs. The expression level of ZO-1 went down in the senescent CECs. Cell viability of senescent CECs was decreased by 70% compared to non-senescent CECs at 0.1 µM of ABT263. The improvement in TEER was consistent with the effect of ABT263 on senescent CECs over time and on day 7, the values reached levels close to control.

Conclusions : We conclude that senescent CECs are responsible for the disruption of barrier function and senolytic drugs are the potential therapeutic approach to protect from the age-related disruption of the epithelial barrier.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.