Corneal toxicity induced by vesicating agents and effective treatment options
Corneal toxicity induced by vesicating agents and effective treatment options
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DOI：
10.1111/nyas.13121
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Agarwal, Rajesh
中科院分区：
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作者：
Goswami, Dinesh G.;Tewari-Singh, Neera;Agarwal, Rajesh
起泡剂硫芥 (SM) 和路易斯 (LEW) 是强效化学战剂，主要对眼睛、皮肤和呼吸系统造成损害。然而，眼组织是最敏感的器官，暴露于疱疹剂会导致双相损伤反应，包括畏光、角膜病变、角膜水肿、溃疡和新生血管形成，并可能导致视力丧失。有几份关于接触 SM 导致眼部损伤的报告，SM 经常在战争中使用。然而，关于LEW造成眼部损伤的报道很少，这表明损伤症状在暴露后立即出现，并且比SM更快。尽管进行了广泛的研究工作，但对于起疱剂引起的眼部损伤（主要是受影响最严重的角膜组织）仍没有有效的治疗方法。因此，我们用SM类似物氮芥建立了原代人角膜上皮细胞和兔角膜器官培养模型，这有助于测试潜在治疗剂的功效。然后，这些药物将针对 SM 和 LEW 诱导的体内角膜损伤模型进行进一步评估，这将有助于开发针对起疱剂引起的眼损伤的潜在广谱疗法。
The vesicating agents sulfur mustard (SM) and lewisite (LEW) are potent chemical warfare agents that primarily cause damage to the ocular, skin, and respiratory systems. However, ocular tissue is the most sensitive organ, and vesicant exposure results in a biphasic injury response, including photophobia, corneal lesions, corneal edema, ulceration, and neovascularization, and may cause loss of vision. There are several reports on ocular injury from exposure to SM, which has been frequently used in warfare. However, there are very few reports on ocular injury by LEW, which indicate that injury symptoms appear instantly after exposure and faster than SM. In spite of extensive research efforts, effective therapies for vesicant-induced ocular injuries, mainly to the most affected corneal tissue, are not available. Hence, we have established primary human corneal epithelial cells and rabbit corneal organ culture models with the SM analog nitrogen mustard, which have helped to test the efficacy of potential therapeutic agents. These agents will then be further evaluated against in vivo SM- and LEW-induced corneal injury models, which will assist in the development of potential broad-spectrum therapies against vesicant-induced ocular injuries.