Departments of Neuroscience and Toxicology, US Army Medical Research Institute of Chemical Defense, Gunpowder, MD.
Cornea. 2020 May;39(5):640-648. doi: 10.1097/ICO.0000000000002278.
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.
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.
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.
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.
眼部暴露于硫芥（SM）蒸气会导致角膜内皮细胞（CEC）急性丧失。在未从 SM 暴露中恢复的眼睛中观察到持续的角膜内皮病变，这表明内皮毒性导致了糜烂性毒剂性角膜炎（MGK）。在这里，我们评估了内皮细胞丢失对 SM 暴露眼睛急性和慢性角膜损伤的贡献。
通过使用 9、11 或 14-mm 蒸气帽，将兔眼体内暴露于等效剂量的 SM。通过临床评估，在 12 周内对暴露面积对角膜损伤进展的影响进行了纵向评估。从 1 天到 12 周，评估了暴露面积对 CEC 形态、内皮和上皮超微结构以及内皮屏障功能的影响。
SM 暴露导致 CEC 丧失和内皮屏障完整性丧失在 1 天，与暴露帽的大小无关。到 3 周时，用 14-mm 蒸气帽暴露的眼睛表现出增加的角膜通透性、由成纤维样形态的细胞再内皮化以及细胞外基质的异常沉积。用 9 或 11-mm 蒸气帽暴露的眼睛表现出短暂的损伤症状，完全缓解，恢复速度与帽的大小相关。
内皮病变大小与发生 MGK 的概率之间的非线性相关性表明，CEC 的丧失是发生 MGK 的决定因素。这些研究说明了内皮修复在预防 MGK 中的重要性。此外，它们排除了基底膜化学修饰作为 MGK 眼睛中反复上皮糜烂的机制原因。
