Kadar T, Turetz J, Fishbine E, Sahar R, Chapman S, Amir A
Department of Pharmacology, Israel Institute for Biological Research, Ness-Ziona, Israel.
Curr Eye Res. 2001 Jan;22(1):42-53. doi: 10.1076/ceyr.22.1.42.6975.
To establish an experimental model for sulfur mustard-induced acute and delayed ocular lesions in rabbits.
Rabbit eyes were exposed to sulfur mustard (HD) vapor (370, 420 microg/l) for a period of two minutes. A three months follow-up study was carried out, based on the evaluation of clinical, biochemical and histological parameters.
HD exposure initiated typical clinical symptoms within 2-6 hrs, characterized by eye closure, eyelid swelling, conjunctival hyperemia, corneal erosions and inflammation. The clinical signs were significantly dose-dependent and reached a peak at 24--72 hrs post exposure. Biochemical evaluation of the aqueous humor exhibited an inflammatory reaction and oxidative stress at 4 hrs after exposure, subsiding at 28 hrs after exposure. Histological examination of corneas at 48 hrs revealed epithelial denudation and marked stromal edema, accompanied by cellular infiltration. Epithelial regeneration started after 72 hrs, and recovery was almost completed within 1--2 weeks, depending on the HD dose. A second phase of pathological processes started as early as two weeks post exposure and was characterized by corneal edema, opacity, recurrent erosions and neovascularization. The delayed injuries were found in 25 and 40% of the eyes respectively, and when appearing, were more severe than the initial ones.
The development of HD-induced ocular lesions in rabbits is similar to the lesions described in human casualties. Quantitative analysis of the various clinical parameters emphasizes the contribution of each tissue to the overall toxic picture. Our experimental model is useful for studying the pathological mechanisms of HD-ocular lesions, and may serve for testing potential therapies.
建立兔芥子气诱导急性和迟发性眼损伤的实验模型。
将兔眼暴露于芥子气(HD)蒸气(370、420微克/升)中两分钟。基于临床、生化和组织学参数的评估进行了为期三个月的随访研究。
HD暴露在2 - 6小时内引发典型临床症状,特征为闭眼、眼睑肿胀、结膜充血、角膜糜烂和炎症。临床体征呈显著剂量依赖性,在暴露后24 - 72小时达到峰值。房水的生化评估显示暴露后4小时出现炎症反应和氧化应激,在暴露后28小时消退。暴露后48小时角膜的组织学检查显示上皮剥脱和明显的基质水肿,伴有细胞浸润。72小时后开始上皮再生,根据HD剂量不同,1 - 2周内基本恢复。病理过程的第二阶段早在暴露后两周开始,特征为角膜水肿、混浊、复发性糜烂和新生血管形成。分别在25%和40%的眼中发现迟发性损伤,一旦出现,比初始损伤更严重。
兔芥子气诱导眼损伤的发展与人伤亡中描述的损伤相似。对各种临床参数的定量分析强调了每个组织对整体毒性情况的作用。我们的实验模型有助于研究HD眼损伤的病理机制,并可用于测试潜在治疗方法。