Effects of chronic alcohol administration on the cornea in preclinical models

Abstract

Purpose : There is a clinical association between acute and chronic alcohol consumption and the incidence of ocular surface disease, including dry eye disease. The goal of this study was to investigate if chronic moderate alcohol consumption leads to signs of DED in vivo, and to investigate oxidative stress pathways involved in alcohol-induced damage to human corneal epithelial cells in vitro.

Methods : Twelve week-old male C57BL/6JRj mice were acclimated to the ad libitum Lieber-DeCarli liquid diet for 5 days. After acclimatization, 5% (vol/vol) ethanol was added to the diet in the alcohol group while control animals were maintained on an isocaloric Lieber-DeCarli liquid diet for 10 days. Corneal fluorescein staining was performed on day 10. Corneal tissue was sectioned and processed for histopathological analysis. For in vitro studies, human corneal epithelial cells (HCE-T; Riken, Japan) were exposed to 0.5% ethanol (vol/vol in media). RNA was collected from cells at 2, 4, 6, and 12 h after ethanol treatment and mRNA levels of oxidative stress markers NFE2L2, HMOX1, and HMOX2 were quantified by qPCR.

Results : Mice who received alcohol exhibited significantly higher corneal fluorescein scores compared to control (median scores: control = 2; alcohol = 3; P<0.001). The average total corneal thickness in the alcohol group was significantly lower than in the control group (74.4 µm and 122.8 µm, respectively; n = 6-7, P<0.05). This reduction was predominantly attributed to a reduction in stromal thickness.
In vitro studies revealed a statistically significant 3-fold increase in NFE2L2 gene expression in response to alcohol treatment in HCE-T cells at 2, 4, and 6 h (P<0.002). There was a trend towards increased HMOX1 expression but no change in expression of the non-inducible HMOX2 isoform.

Conclusions : Our data provide the first preclinical evidence that chronic moderate alcohol consumption can lead to pathological signs of ocular surface disease in vivo. In vitro, alcohol exposure causes activation of Nrf2-mediated oxidative stress pathways. Future studies will investigate the effects of alcohol on corneal barrier function and the implications of chronic moderate vs. binge alcohol use.

This is a 2021 ARVO Annual Meeting abstract.