Abstract
Purpose :
Chloropicrin (CP) is a choking and lacrimating agent, mainly used as an agricultural pesticide and fumigant against various nematodes and insects. However, CP was used in World War I as a chemical warfare agent and multiple recent warfare, accidental and occupational exposures have been reported. There are no treatment options against CP-induced injuries. Although sex differences play a role in corneal injury and wound healing, the role of sex differences in the context of CP-induced corneal injury in a relevant injury model has not been studied. Using markers of CP-induced corneal injury, we hypothesized that following exposure, CP results in an exacerbated corneal injury, with delayed corneal wound healing in male mice compared to female mice.
Methods :
The left eye of male and female Balb/C mice was exposed to CP [10% CP for 1 min (~0.7652ppb)] using a vapor cap exposure system and the right eye served as a control. Clinical assessment using a slit lamp microscope and scoring system was carried out at 3-, 6- hours, and at 1-, 3-, 7-, 14-, 28-days post CP exposure. Mice were euthanized at day 1 and day 7 post CP exposure, and the eyes were harvested to be processed and stained using a H and E staining technique. Samples entailed 3-10 mice per time point/group. Severity of clinical injuries was evaluated using a modified SPOT scoring system by two independent blinded observer and the average reported. Using GraphPad, results were analyzed using 2-way-ANOVA statistical analysis method.
Results :
Clinical assessment indicated a significant increase in eyelid edema in male mice exposed to CP, but no female mice showed eyelid swelling throughout the experiment. Corneal ulceration was significantly higher in female mice on 7- and 28-days post CP exposure compared to male mice. There was a rapid degradation of the epithelial layer on day 1, and a rapid regeneration of the epithelial layer on day 7 in male mice compared to female mice. Evaluation of stromal thickness indicated significant difference in the increase in corneal stromal thickness in male mice compared to female mice.
Conclusions :
Although results from this study does not completely support our hypothesis, it provides relevant data on the role of sex difference in CP-induced corneal injury. Since both male and female population are at risk of CP exposure, further mechanistic studies to evaluate differences in the mechanism of CP in corneal injury is needed.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.