Characterization of the rabbit conjunctiva: Effects of sulfur mustard

Exp Mol Pathol. 2021 Aug;121:104656. doi: 10.1016/j.yexmp.2021.104656. Epub 2021 Jun 1.

Abstract

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.

Keywords: Eyelids; Goblet cells; Mucin 1; Mucin 4; Mucin 5ac; Vesicants.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chemical Warfare Agents / toxicity*
  • Conjunctiva / drug effects
  • Conjunctiva / metabolism
  • Conjunctiva / pathology*
  • Cornea / drug effects
  • Cornea / metabolism
  • Cornea / pathology*
  • Epithelium / drug effects
  • Epithelium / metabolism
  • Epithelium / pathology*
  • Goblet Cells / drug effects
  • Goblet Cells / metabolism
  • Goblet Cells / pathology*
  • Male
  • Mucin-1 / metabolism
  • Mucin-4 / metabolism
  • Mustard Gas / toxicity*
  • Rabbits

Substances

  • Chemical Warfare Agents
  • Mucin-1
  • Mucin-4
  • Mustard Gas