Primary cultures of rabbit corneal epithelial cells as an experimental model to evaluate ocular toxicity and explore modes of action of toxic injury.

In vivo and in vitro animal models are used to investigate the toxicological modes of action of a substance as surrogates for humans since it is not ethical to conduct certain experiments in humans. The toxic actions of many compounds are manifested in specific organs, known as target organs of toxicity. Thus, in vitro systems that use cells derived from that target organ are best used to understand toxicological mechanisms. This article reviews the development of primary cultures of rabbit corneal epithelial cells which retain tissue specific and functional properties of in vivo cells as an experimental in vitro model to study ocular toxicity. This model system was used to evaluate initial ocular toxicity and mode of action of cocaine, tetracaine, and proparacaine, widely used local anesthetics. Initial toxicity and toxicity rankings of eight surfactants were determined using four different cytotoxicity endpoints. In addition, modes of action of delayed and prolonged cell injury after CE cells were treated with benzalkonium chloride, a cationic surfactant, and sodium dodecyl sulfate, an anionic surfactant, were investigated at multiple postexposure times after a 1-h treatment. The two surfactants produced distinctly different prolonged effects on cultured corneal epithelial cells, which may suggest these surfactants differentially affect cellular recovery.