Dept. Of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100, Israel.
Dept. Of Pharmacology, Israel Institute for Biological Research, Ness Ziona, 74100, Israel.
Toxicol Lett. 2019 Oct 10;314:153-163. doi: 10.1016/j.toxlet.2019.08.002. Epub 2019 Aug 10.
Eye exposure to organophosphate (OP) chemical warfare irreversible acetylcholinesterase inhibitors, results in long-term miosis and impaired visual function. In contrast to the well-documented miotic and ciliary muscle spasm observed following chemical warfare, OP ocular exposure, little is known regarding the ocular surface histopathological insult. The aim of the present study was to determine the degree of the ocular surface insult following sarin or VX ocular exposure and to evaluate potential anti-cholinergic treatments in counteracting this insult. Rats that were whole body exposed to various sarin concentrations (0.049-43 μg/L; 5 min exposure), showed a dose-dependent miotic response and light reflex impairment. Following whole body sarin exposure, a dose dependent ocular surface histopathological insult was developed. A week following exposure to a low concentration of 0.05 μg/L, conjunctival pathology was observed, while corneal insult was noticed only following exposure to a concentration of 0.5 μg/L and above. Both tissues presented poorer outcomes when exposed to higher sarin concentrations. In contrast, eyes topically exposed to 1 μg sarin demonstrated no ocular insult a week following exposure. On the contrary, topical exposure to 1 μg VX resulted in a significant corneal insult. Anticholinergic treatments such as 0.1% atropine or 2% homatropine, given shortly following VX exposure, counteracted this insult. The results of this study show that not only do anti-cholinergic treatments counteract the miotic response, but also prevent the histopathological insult observed when given shortly following OP exposure.
眼部接触有机磷（OP）化学战不可逆乙酰胆碱酯酶抑制剂会导致长期瞳孔缩小和视觉功能受损。与化学战中观察到的明显的瞳孔缩小和睫状肌痉挛不同，OP 眼部暴露后，人们对眼表组织病理学损伤知之甚少。本研究旨在确定沙林或 VX 眼部暴露后眼表损伤的程度，并评估潜在的抗胆碱能治疗方法对抗这种损伤的作用。全身暴露于不同沙林浓度（0.049-43μg/L；5 分钟暴露）的大鼠表现出剂量依赖性的瞳孔缩小反应和光反射损伤。全身暴露于沙林后，眼表出现剂量依赖性的组织病理学损伤。暴露于低浓度 0.05μg/L 后一周，观察到结膜病变，而仅在暴露于 0.5μg/L 及以上浓度时才观察到角膜损伤。两种组织在暴露于更高的沙林浓度时表现出更差的结果。相比之下，眼部局部暴露于 1μg 沙林一周后未见眼表损伤。相反，局部暴露于 1μg VX 会导致明显的角膜损伤。抗胆碱能治疗，如暴露于 VX 后不久给予 0.1%阿托品或 2%氢溴酸东莨菪碱，可对抗这种损伤。本研究结果表明，抗胆碱能治疗不仅能对抗瞳孔缩小反应，还能预防 OP 暴露后不久观察到的组织病理学损伤。
