Lipidomic analysis of human corneal epithelial cells exposed to ocular irritants highlights the role of phospholipid and sphingolipid metabolisms in detergent toxicity mechanisms

Abstract

Detergent chemicals, widely used in household products, in pharmaceutical, medical, cosmetic and industrial fields, have been linked to side effects and involved in several eye diseases. On the ocular surface, detergents can interfere with the corneal epithelium, the most superficial layer of the cornea, representing a line of defence against external aggression. Despite its major role in numerous biological functions, there is still little data regarding disruption of lipid homeostasis induced by ocular irritants. To this purpose, a lipidomic analysis using UPLC-HRMS/MS-ESI ± was performed on human corneal epithelial (HCE) cells incubated with three widely known ocular irritants: benzalkonium chloride (BAK), sodium lauryl sulfate (SLS) and Triton X-100 (TXT). We found that these ocular irritants lead to a profound modification of the HCE cell lipidome. Indeed, the cell content of ceramide species increased widely while plasmalogens containing polyunsaturated fatty acid species, especially docosahexaenoic acids, decreased. Furthermore, these irritants upregulated the activity of phospholipase A₂. The present study demonstrates that BAK, SLS and TXT induced disruption of the cell lipid homeostasis, highlighting that lipids mediate inflammatory and cell death processes induced by detergents in the cornea. Lipidomics may thus be regarded as a valuable tool to investigate new markers of corneal damage.

Keywords: Cell toxicology; Detergents; Lipid homeostasis; Lipidomics; Ocular irritants; PLA(2).