Dachir Shlomit, Gutman Hila, Gore Ariel, Cohen Liat, Cohen Maayan, Amir Adina, Horwitz Vered, Kadar Tamar
Department of Pharmacology, Israel Institute for Biological Research, Ness-Ziona, Israel.
Cornea. 2017 Aug;36(8):980-987. doi: 10.1097/ICO.0000000000001234.
Ocular injuries after exposure to sulfur mustard (SM) are characterized by acute corneal erosion and inflammation of the anterior segment that may be followed by delayed corneal neovascularization and epithelial defects, associated with limbal stem cell deficiency in part of the exposed eyes. This study aimed to further clarify the mechanism of the late injury by monitoring SM-induced cytological alterations in the ocular surface, in relation to the clinical symptoms, using impression cytology (IC).
Rabbit eyes were exposed to SM vapor (n = 20) and were clinically observed up to 4 weeks. Samples for IC were collected simultaneously from the upper bulbar conjunctiva, limbus, and cornea and then fixed and stained with periodic acid-Schiff and hematoxylin. At 1 month, animals were killed and eyes dissected and processed for histology.
Concomitant with clinical symptoms of SM ocular toxicity, IC showed significant long-term loss of conjunctival goblet cells shortly after exposure, followed by abnormal differentiation toward squamous metaplasia. Simultaneously with corneal erosion, apoptotic bodies and cellular debris were seen in the corneal epithelium, followed by regeneration at 1 week. Migration of conjunctival goblet cells toward the cornea was noted in neovascularized eyes, as early as 1 week, indicating limbal stem cell deficiency. The IC findings were supported by histological evaluation.
Continuous monitoring of the ocular surface after SM exposure by IC enables earlier detection of pathology and therapeutic intervention, therefore, is recommended for routine follow-up of casualties. Prolonged loss of goblet cells may point toward the role of mucin in the pathogenesis.
接触硫芥（SM）后的眼部损伤特征为急性角膜糜烂和眼前节炎症，随后可能出现延迟性角膜新生血管形成和上皮缺损，部分暴露眼伴有角膜缘干细胞缺乏。本研究旨在通过使用印迹细胞学（IC）监测SM诱导的眼表细胞学改变，以进一步阐明晚期损伤的机制，并将其与临床症状相关联。
将兔眼暴露于SM蒸气（n = 20），并进行长达4周的临床观察。同时从上睑结膜、角膜缘和角膜采集IC样本，然后用高碘酸 - 希夫试剂和苏木精固定染色。在1个月时，处死动物，解剖眼睛并进行组织学处理。
与SM眼部毒性的临床症状同时出现的是，IC显示暴露后不久结膜杯状细胞长期显著减少，随后向鳞状化生异常分化。与角膜糜烂同时，在角膜上皮中可见凋亡小体和细胞碎片，随后在1周时再生。早在1周时，在新生血管化的眼中就注意到结膜杯状细胞向角膜迁移，表明角膜缘干细胞缺乏。IC结果得到组织学评估的支持。
通过IC对SM暴露后的眼表进行连续监测能够更早地检测病理变化并进行治疗干预，因此，建议用于伤亡人员的常规随访。杯状细胞的长期减少可能表明粘蛋白在发病机制中的作用。
