Corneal Endothelial Cell Toxicity Determines Long-Term Outcome After Ocular Exposure to Sulfur Mustard Vapor.
| Autor: | McNutt PM; Departments of Neuroscience and Toxicology, US Army Medical Research Institute of Chemical Defense, Gunpowder, MD., Nguyen DL, Nelson MR, Lyman ME, Eisen MM, Ondeck CA, Wolfe SE, Pagarigan KT, Mangkhalakhili MC, Kniffin DM, Hamilton TA |
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| Jazyk: | angličtina |
| Zdroj: | Cornea [Cornea] 2020 May; Vol. 39 (5), pp. 640-648. |
| DOI: | 10.1097/ICO.0000000000002278 |
| Abstrakt: | Purpose: Ocular exposure to sulfur mustard (SM) vapor causes acute loss of corneal endothelial cells (CECs). Persistent corneal endothelial pathologies are observed in eyes that do not recover from SM exposure, suggesting that endothelial toxicity contributes to mustard gas keratopathy (MGK). Here, we evaluated the contributions of endothelial loss to acute and chronic corneal injuries in SM-exposed eyes. Methods: Rabbit eyes were exposed in vivo to equivalent doses of SM using 9-, 11-, or 14-mm vapor caps. The effects of exposure area on corneal injury progression were longitudinally evaluated over 12 weeks using clinical evaluations. The effects of exposure area on CEC morphology, endothelial and epithelial ultrastructure, and endothelial barrier function were determined from 1 day to 12 weeks. Results: SM exposure caused loss of CECs and failure of endothelial barrier integrity at 1 day, independent of exposure cap size. By 3 weeks, eyes exposed with the 14-mm vapor cap exhibited increased corneal permeability, repopulation of the endothelium by cells with fibroblastic morphology, and abnormal deposition of extracellular matrix. Eyes exposed with 9- or 11-mm vapor caps exhibited transient symptoms of injury that fully resolved, with the rate of recovery correlated with cap size. Conclusions: The nonlinear correlation between endothelial lesion size and probability of developing MGK suggests that the CEC loss is a determinative factor for emergence of MGK. These studies illustrate the importance of endothelial repair in preventing MGK. Furthermore, they exclude chemical modification of basement membrane as a mechanistic cause of recurrent epithelial erosions in MGK eyes. |
| Databáze: | MEDLINE |
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