Unveiling the acute toxic pathology and transcriptomic signature of ocular exposure to phosgene oxime using an in vivo mouse model: A novel pilot study.

Abstract

Phosgene oxime (CX), a toxic nettle and highly dangerous urticating vesicant, is a potential chemical threat agent. Exposure to CX is a concern due to its penetrative property, resulting in immediate damage to the skin, lungs, and eye tissues. Although the eye is the most sensitive organ to chemical exposures including CX, there is a lack of research on CX, with a knowledge gap on its toxic effects and the mechanism(s) of ocular injuries. This novel pilot study investigated the toxic pathophysiological effects of CX exposure in mouse ocular tissue. The eyeballs of C57BL/6 mice were either unexposed (sham) or exposed to CX for 15 or 30 s, and eyes were collected for assessments 24 h after exposure, following euthanasia. CX exposure caused a significant degradation of the corneal epithelial layer, increased cellularity of the corneal stroma, loss of endothelial cells, and indicated damage to the ciliary body, lens, and the retina. RNA sequencing using DESeq2 (p-value ≤0.01 and |log2-Fold Change| ≥ 1) identified 697 downregulated and 233 upregulated genes after ocular CX exposure. Functional pathway enrichment using Kyoto Encyclopedia of Genes and Genomes pathway enrichment revealed upregulation of pathways mainly related to inflammation (including cytokines) and cell death including ferroptosis, and downregulation of pathways mainly related to metabolism and tight junction, This pilot study will facilitate in designing further comprehensive studies aimed at, developing relevant CX-induced acute and delayed ocular injury models, and in identifying injury biomarkers and associated mechanisms.