Pathogenesis of acute and delayed corneal lesions after ocular exposure to sulfur mustard vapor.
OBJECTIVE
Sulfur mustard (SM) exposure results in dose-dependent morbidities caused by cytotoxicity and vesication. Although lesions resulting from ocular exposure often resolve clinically, an idiopathic delayed mustard gas keratopathy (MGK) can develop after a moderate or severe exposure. Sequelae include persistent keratitis, recurring epithelial lesions, corneal neovascularization, and corneal degeneration, which can lead to impaired vision or loss of sight. The purpose of this effort is to correlate structural changes with injury progression during the development of MGK.


METHODS
New Zealand White rabbit corneas were exposed to SM using a vapor cup delivery system. The transition from acute to delayed injury was characterized by clinical, histological, and ultrastructural metrics over 8 weeks.


RESULTS
Exposure dose was correlated to the likelihood of developing MGK but not to its severity. In a 56-animal cohort, a 2.5-minute exposure generated a corneal lesion, with 89% of corneas developing MGK within 5 weeks. A significant decrease in corneal edema at 2 weeks was predictive of the 11% of corneas that underwent asymptomatic recovery. Ultrastructural comparison of asymptomatic and MGK corneas at 8 weeks indicates that MGK is characterized by persistent edema and profound disorganization of the basement membrane zone.


CONCLUSIONS
Ultrastructural changes associated with the delayed pathophysiology of corneal SM vapor exposure involve severe degeneration of the basement membrane zone and persistent edema. The mechanisms underlying MGK pathogenesis seem to alter injury progression as soon as 2 weeks after exposure. These data suggest that the vapor cup model system is suitable for therapeutic evaluation.
United States Army Medical Research Institute of Chemical Defense, Gunpowder, MD 21010, USA. patrick.mcnutt@us.army.mil
Patrick
P
McNutt
Tracey
T
Hamilton
Marian
M
Nelson
Angela
A
Adkins
Adam
A
Swartz
Richard
R
Lawrence
Denise
D
Milhorn
D000208:Acute Disease; D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D003316:Corneal Diseases / Q000139:chemically induced* / Q000473:pathology*; D015715:Corneal Edema / Q000139:chemically induced / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D008401:Gas Chromatography-Mass Spectrometry; D009151:Mustard Gas / Q000633:toxicity*; D011817:Rabbits
D002619:Chemical Warfare Agents; D009151:Mustard Gas