Abstract
Purpose :
Chloropicrin (CP), a choking and lacrimating agent, has been used as a warfare chemical agent, mainly during World War I. It is currently a popular pesticide, facilitating its easy acquisition and potential use as a chemical threat agent in addition to its accidental and occupational exposures. Exposure to CP results in severe ocular injury; however, studies on ocular injury progression and underlying mechanisms in a relevant in vivo animal model are lacking deterring the development of effective therapies. This study tested the hypothesis that CP exposure results in clinical and biological injury to corneal epithelia, stroma and endothelial layers.
Methods :
The left eye of male BALB/c mice were exposed to CP using a vapour cap [20% CP for 1 min or 30 sec (0.4 mg of CP) or 10% CP for 1 min (0.2 mg of CP)], and the right eye served as a control. Clinical assessment was done from day 1 to 25 post-exposure. Mice were euthanized at day 25 post-CP exposure, and the eyes were harvested to analyze for biological markers.
Results :
At all concentrations, CP-exposures caused a significant increase in corneal ulceration and eyelid oedema, which resolved by day 14 post-exposure. However, CP exposure caused a significant unresolved increase in corneal opacity and neovascularization. Development of corneal hydrops and hyphemia was observed as advanced CP effects. Histopathological analyses showed a significant CP-induced decrease in corneal epithelial thickness and increased stromal thickness with stromal fibrosis, oedema, neovascularization, loss of the corneal endothelial cells, breaks in Descemet membrane, anterior and posterior synechia and infiltration of immune cells.
Conclusions :
CP caused severe ocular injury mainly to the cornea. Loss of the corneal endothelial cells and breaks in Descemet membrane could be associated with corneal oedema causing hydrops that can contribute to the cloudy vision, corneal scarring, and eye pain. Damage to the uveal vessels might be further responsible for corneal opacity and hyphemia. Although exposure to 20% CP for 1 min caused more eyelid oedema, ulceration and hyphemia, other effects were similar in all CP exposures. These novel findings following CP ocular exposure in a mouse will be helpful in model development and pathophysiological studies to identify the mechanism of CP-induced ocular injury and molecular targets for therapeutic interventions.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.