Acute ocular effects of mustard gas: ultrastructural pathology and immunohistopathology of exposed rabbit cornea.
Whole-body exposure to sulfur mustard (HD) produces cutaneous, respiratory and ocular impairment. Of these, ocular damage causes the most immediate incapacitation. Heretofore, characterization of HD ocular toxicity has been largely limited to gross and histological observations. In the present study we explore histological, ultrastructural and immunopathological acute effects of HD ocular exposure and establish correlations with HD toxicity data already documented for dermal exposure. Anesthetized rabbits were exposed to 0.4 microl of liquid HD placed directly on the cornea. Animals were euthanized at 6, 9 and 24 h post-exposure and the eyes were enucleated and processed for histopathology, ultrastructural and immunoperoxidase study. At 6 and 9 h, the most prominent histological feature was nuclear pyknosis, necrosis and loss of polarity of corneal epithelial basal cells to the exclusion of other epithelial cells. At 24 h, all corneal epithelial cells presented degenerative changes, with the epithelium eventually detaching from the underlying basement membrane at the level of the lamina lucida. Microblisters, a characteristic HD-induced skin pathology of the basement membrane zone of animals, were absent in this corneal study. Edema, degenerating fibroblasts and inflammatory cellular infiltrates were persistent stromal responses. Immunopathological effects included changes in antigenicity of bullous pemphigoid protein, laminin, desmosonal protein, Ki67 and p53. These morphological and immunopathological effects of corneal exposure to HD appear to be largely consistent with that previously reported for dermal exposures, perhaps providing shared anatomical considerations for the development of specific HD prophylaxis and therapy.
Petrali
J P
JP
Comparative Medicine and Drug Assessment Divisions, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425, USA.
Dick
E J
EJ
Brozetti
J J
JJ
Hamilton
T A
TA
Finger
A V
AV
D000279:Administration, Cutaneous; D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D003315:Cornea / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D003879:Dermatologic Agents / Q000633:toxicity*; D004487:Edema; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005347:Fibroblasts; D007249:Inflammation; D009151:Mustard Gas / Q000633:toxicity*; D009336:Necrosis; D011817:Rabbits
D003879:Dermatologic Agents; D009151:Mustard Gas