Modulation of the canonical Wnt pathway by Benzalkonium Chloride in corneal epithelium

national Natural Science Foundation of China (NSFC) [30872810]; NSFC-RGC [30931160432]Benzalkonium Chloride (BAC) is commonly used in eyedrops. Although the cytotoxicity of BAC has been reported, the mechanism underlying its toxic effect has not been elucidated. The present study investigated the role of the Wnt signaling pathway in the cytotoxicity of BAC in corneal epithelial cells and in the rat cornea. We demonstrated that phosphorylation of beta-catenin, a downstream effector of the canonical Wnt pathway, was down-regulated by a short exposure to BAC in both cultured human corneal epithelial cells (HCE) and a cultured mouse corneal epithelial progenitor cell line (TKE2), suggesting an activation of the Wnt pathway. The activation of Wnt pathway inhibitor, secreted frizzled-related protein-1 (sFRP1), reversed BAC-induced down-regulating effects on the level of phosphorylation of beta-catenin and ameliorated cell viability in cells treated with BAC. In the rat cornea, the levels of total beta-catenin were significantly up-regulated 8 h after the topical administration of BAC. Taken together, these results provided novel evidence suggesting that the cytotoxicity of BAC may be mediated through modulation of the Wnt pathway. (C) 2011 Published by Elsevier Ltd