Progression of ocular sulfur mustard injury: development of a model system.
Exposure of tissues to sulfur mustard (SM) results in the formation of protein and nucleotide adducts that disrupt cellular metabolism and cause cell death. Subsequent pathologies involve a significant proinflammatory response, disrupted healing, and long-term defects in tissue architecture. Following ocular exposure, acute corneal sequelae include epithelial erosions, necrosis, and corneal inflammation. Longer term, a progressive injury becomes distributed throughout the anterior chamber, which ultimately causes a profound remodeling of corneal tissues. In many cases, debilitating and vision-threatening injuries reoccur months to years after the initial exposure. Preliminary data in humans suffering from chronic epithelial lesions suggest that thymosin beta4 (Tbeta4) may be a viable candidate to mitigate acute or long-term ocular SM injury. To evaluate therapeutic candidates, we have developed a rabbit ocular exposure model system. In this paper, we report molecular, histological, ultrastructural, and clinical consequences of rabbit ocular SM injury, which can be used to assess Tbeta4 efficacy, including timepoints at which Tbeta4 will be assessed for therapeutic utility.
United States Army Medical Research and Materiel Command, Fort Detrick, Maryland, USA.
Denise
D
Milhorn
Tracey
T
Hamilton
Marian
M
Nelson
Patrick
P
McNutt
D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D005123:Eye; D005131:Eye Injuries / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D009151:Mustard Gas / Q000494:pharmacology* / Q000627:therapeutic use; D009336:Necrosis / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D010829:Physiological Phenomena; D011817:Rabbits; D013947:Thymosin / Q000627:therapeutic use*; D014945:Wound Healing; D000099201:Thymosin beta(4)
D009151:Mustard Gas; D013947:Thymosin; D000099201:Thymosin beta(4)