title: Structural, morphological, and functional correlates of corneal endothelial toxicity following corneal exposure to sulfur mustard vapor.
abstract: OBJECTIVE
  Sulfur mustard (SM) is a highly reactive vesicant that causes severe ocular injuries. Following exposure to moderate or high doses, a subset of victims develops a chronic injury known as mustard gas keratopathy (MGK) involving a keratitis of unknown etiopathogenesis with secondary keratopathies such as persistent epithelial lesions, corneal neovascularization, and progressive corneal degeneration. This study was designed to determine whether SM exposure evokes acute endothelial toxicity and to determine whether endothelial pathologies were specifically observed in MGK corneas as opposed to healed corneas.
  
  
  METHODS
  Corneas of New Zealand white rabbits were exposed to SM vapor, and the corneal endothelium was evaluated at 1 day and 8 weeks using scanning electron microscopy (SEM), transmission electron microscopy (TEM), in vivo confocal microscopy (IVM), and fluorescent microscopy. Barrier function was measured by uptake of a fluorescent dye injected into the anterior chamber.
  
  
  RESULTS
  A centripetal endothelial injury at 1 day was observed by SEM, TEM, IVM, and fluorescent microscopy. In vivo confocal microscopy revealed additional cytotoxicity between 1 and 13 days. In contrast to healed corneas, which appeared similar to sham-exposed naive eyes at 8 weeks, MGK corneas exhibited significant evidence of continued pathological changes in the endothelium.
  
  
  CONCLUSIONS
  Endothelial toxicity occurs at the right time and with the appropriate pathophysiology to contribute to MGK. Based on these findings, we propose a model that explains the relationships among SM dose, the biphasic progression, and the various clinical trajectories of corneal SM injury and that provides a mechanism for temporal variations in MGK onset. Finally, we discuss the implications for the management of SM casualties.
authors.affiliation: United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Grounds, Maryland.
authors.forename: Patrick
authors.initials: P
authors.lastname: McNutt
authors.forename: Kaylie
authors.initials: K
authors.lastname: Tuznik
authors.forename: Marian
authors.initials: M
authors.lastname: Nelson
authors.forename: Angie
authors.initials: A
authors.lastname: Adkins
authors.forename: Megan
authors.initials: M
authors.lastname: Lyman
authors.forename: Elliot
authors.initials: E
authors.lastname: Glotfelty
authors.forename: James
authors.initials: J
authors.lastname: Hughes
authors.forename: Tracey
authors.initials: T
authors.lastname: Hamilton
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000493:pharmacokinetics / Q000633:toxicity; D003316:Corneal Diseases / Q000139:chemically induced / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004728:Endothelium, Corneal / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D005131:Eye Injuries / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D005260:Female; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D009151:Mustard Gas / Q000493:pharmacokinetics / Q000633:toxicity*; D011817:Rabbits
chemical_list: D002619:Chemical Warfare Agents; D009151:Mustard Gas
keywords: corneal edema; corneal endothelial cells; mustard gas; mustard gas keratopathy; sulfur mustard