United States Army Medical Research Institute of Chemical Defense, Gunpowder, MD 21010, USA.
Cornea. 2012 Mar;31(3):280-90. doi: 10.1097/ICO.0B013E31823D02CD.
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.
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.
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.
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.
芥子气（SM）暴露会导致细胞毒性和起疱作用引起的剂量依赖性疾病。尽管眼部暴露引起的病变通常在临床上得到解决，但中度或重度暴露后可能会发生特发性延迟性芥子气角膜炎（MGK）。后遗症包括持续性角膜炎、复发性上皮病变、角膜新生血管形成和角膜变性，这可能导致视力受损或失明。本研究旨在在 MGK 发展过程中，将结构变化与损伤进展相关联。
使用蒸气杯输送系统使新西兰白兔角膜暴露于 SM。通过临床，组织学和超微结构指标，在 8 周内对从急性损伤到延迟性损伤的转变进行了特征描述。
暴露剂量与发生 MGK 的可能性相关，但与严重程度无关。在 56 只动物的队列中，2.5 分钟的暴露会产生角膜病变，其中 89％的角膜在 5 周内发生 MGK。第 2 周角膜水肿明显减少预示着 11％的角膜会无症状恢复。第 8 周无症状和 MGK 角膜的超微结构比较表明，MGK 的特征是持续的水肿和基膜区严重紊乱。
与角膜 SM 蒸气暴露的迟发性病理生理学相关的超微结构变化涉及基膜区的严重退化和持续的水肿。MGK 发病机制的机制似乎在暴露后仅 2 周就改变了损伤进展。这些数据表明蒸气杯模型系统适合于治疗评估。
