Abstract
Purpose :
Vesicating chemicals like Sulphur mustard (SM) or Nitrogen Mustard (NM) can cause devastating damage to the eyes, skin, and lungs. Eyes, being the most sensitive among them, have complications that can manifest immediately after exposure (acute) and can last for years (chronic). There is no FDA-approved drug available to be used as Medical Counter Measures (MCM) against such injuries. Further understanding of the acute and chronic response of the eye is essential for developing MCM candidates, which needs the development and characterization of relevant injury models. The purpose of this study was to develop and characterize a mouse model of ocular surface injury.
Methods :
The ocular surface of 10-12 weeks C57/BL6 mice were treated with 2% (w/v) NM solution for 5 min to develop the mouse model of NM-induced ocular surface injury. Same-age littermates treated with saline served as controls. The model was extensively characterized by clinical and histopathological analysis of the ocular surface, quantitative analysis of the inflammatory markers and bioactive sphingolipids, and visual and retinal functions at both acute and chronic phases of the injury.
Results :
We observed severe inflammation of the eye, resulting in structural deformity of the corneal epithelium and stroma. The NM-treated mice have significantly diminished visual and retinal functions, starting at the acute phase and continuing through the chronic phases compared to the saline-treated mice. We observed an alteration of the inflammatory markers and their expression at different phases of the injury that coincided with an increase in the levels of the bioactive sphingolipid Ceramide. We also observed a reduction in sphingomyelin (SM) levels with increased activity of the enzyme acidic sphingomyelinase (aSMase) in the acute phase of the injury.
Conclusions :
The novel mouse model can recapitulate the injuries reported in human and rabbit models of SM or NM injury. NM exposure leads to severe inflammation, causing irreversible alterations to the corneal structure that compromise the vision. The results also suggest an intricate interplay between inflammatory markers over the injury period and alteration in sphingolipid homeostasis that help in the manifestation of the ocular surface injury as a result of NM exposure.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.