Development of mouse models for the study of chloropicrin and hydrogen fluoride ocular injury.

The possibility of chemical terrorism within the United States is a rising concern, with the eye being one of the most sensitive tissues to toxicant exposure. We sought to develop mouse models of toxicant-induced ocular injury for the purpose of evaluating potential therapeutics. Chloropicrin (CP) and hydrogen fluoride (HF) were selected for the study owing to their reportedly high potential to induce ocular injury. Eyes of female BALB/c mice were exposed to CP or HF vapor in order to produce a moderate injury, as defined by acute corneal epithelial loss followed by progressive corneal pathology with the absence of injury to deeper eye structures. Clinical injury progression was evaluated up to 12 weeks postexposure, where a significant dose-dependent induction of corneal neovascularization was measured. Histopathology noted epithelial necrosis and stromal edema as early as 24 h after exposure but was resolved by 12 weeks. A significant increase in inflammatory cytokine concentrations was measured in the cornea 24 h after exposure and returned to baseline by day 14. The ocular injury models we developed here for CP and HF exposure should serve as a valuable tool for the future evaluation of novel therapeutics and the molecular mechanisms of injury.