Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, United States.
Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, United States.
Exp Mol Pathol. 2021 Aug;121:104656. doi: 10.1016/j.yexmp.2021.104656. Epub 2021 Jun 1.
Sulfur mustard (SM; bis (2-chloroethyl) sulfide) is a potent vesicant which causes irritation of the conjunctiva and damage to the cornea. In the present studies, we characterized the ocular effects of SM in New Zealand white rabbits. Within one day of exposure to SM, edema and hazing of the cornea were observed, followed by neovascularization which persisted for at least 28 days. This was associated with upper and lower eyelid edema and conjunctival inflammation. The conjunctiva is composed of a proliferating epithelium largely consisting of stratified columnar epithelial cells overlying a well-defined dermis. Superficial layers of the conjunctival epithelium were found to express keratin 1, a marker of differentiating squamous epithelium, while in cells overlying the basement membrane expressed keratin 17, a marker of stratified squamous epithelium. SM exposure upregulated keratin 17 expression. Mucin 5 ac producing goblet cells were interspersed within the conjunctiva. These cells generated both acidic and neutral mucins. Increased numbers of goblet cells producing neutral mucins were evident after SM exposure; upregulation of expression of membrane-associated mucin 1 and mucin 4 in the superficial layers of the conjunctival epithelium were also noted. These data demonstrate that ocular exposure of rabbits to SM causes significant damage not only to the cornea, but to the eyelid and conjunctiva, suggesting multiple targets within the eye that should be assessed when evaluating the efficacy of potential countermeasures.
硫芥(SM;双(2-氯乙基)硫醚)是一种强效的糜烂性毒剂,会刺激结膜并损伤角膜。在本研究中,我们对新西兰白兔的眼部 SM 损伤效应进行了特征描述。暴露于 SM 后 1 天内,观察到角膜水肿和混浊,随后出现至少持续 28 天的新生血管化。这与上、下眼睑水肿和结膜炎症有关。结膜由增殖的上皮组成,主要由复层柱状上皮细胞覆盖,下有明确的真皮。结膜上皮的浅层表达角蛋白 1,这是分化的鳞状上皮的标志物,而上皮基底膜上方的细胞表达角蛋白 17,这是复层鳞状上皮的标志物。SM 暴露可上调角蛋白 17 的表达。粘蛋白 5 产生的杯状细胞散布在结膜中。这些细胞产生酸性和中性粘蛋白。SM 暴露后,产生中性粘蛋白的杯状细胞数量增加;在上皮浅层,膜相关粘蛋白 1 和粘蛋白 4 的表达也上调。这些数据表明,兔子眼部暴露于 SM 不仅会导致角膜严重损伤,还会导致眼睑和结膜损伤,这提示在评估潜在对策的效果时,应评估眼部的多个靶标。