4.5 Article

Characterization of the rabbit conjunctiva: Effects of sulfur mustard

Journal

EXPERIMENTAL AND MOLECULAR PATHOLOGY
Volume 121, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yexmp.2021.104656

Keywords

Vesicants; Goblet cells; Mucin 5ac; Mucin 1; Mucin 4; Eyelids

Categories

Funding

  1. U.S. Department of Health and Human Services, National Institutes of Health [AR055073, ES005022, R25ES020721]

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Exposure of rabbits to sulfur mustard (SM) causes significant damage to the cornea, eyelid, and conjunctiva, including edema, haze, neovascularization, and inflammation. The expression of keratin 1 and keratin 17 in the conjunctival epithelium is upregulated after SM exposure, along with an increase in goblet cells producing neutral mucins. This indicates multiple targets within the eye should be assessed when evaluating potential countermeasures for SM exposure.
Sulfur mustard (SM; bis (2-chloroethyl) sulfide) is a potent vesicant which causes irritation of the conjunctiva and damage to the cornea. In the present studies, we characterized the ocular effects of SM in New Zealand white rabbits. Within one day of exposure to SM, edema and hazing of the cornea were observed, followed by neovascularization which persisted for at least 28 days. This was associated with upper and lower eyelid edema and conjunctival inflammation. The conjunctiva is composed of a proliferating epithelium largely consisting of stratified columnar epithelial cells overlying a well-defined dermis. Superficial layers of the conjunctival epithelium were found to express keratin 1, a marker of differentiating squamous epithelium, while in cells overlying the basement membrane expressed keratin 17, a marker of stratified squamous epithelium. SM exposure upregulated keratin 17 expression. Mucin 5 ac producing goblet cells were interspersed within the conjunctiva. These cells generated both acidic and neutral mucins. Increased numbers of goblet cells producing neutral mucins were evident after SM exposure; upregulation of expression of membrane-associated mucin 1 and mucin 4 in the superficial layers of the conjunctival epithelium were also noted. These data demonstrate that ocular exposure of rabbits to SM causes significant damage not only to the cornea, but to the eyelid and conjunctiva, suggesting multiple targets within the eye that should be assessed when evaluating the efficacy of potential countermeasures.

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