Ocular surface histopathological insult following sarin and VX exposure and potential treatments in the rat model

Toxicol Lett. 2019 Oct 10:314:153-163. doi: 10.1016/j.toxlet.2019.08.002. Epub 2019 Aug 10.

Abstract

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.

Keywords: Anticholinergic treatments; Atropine; Cornea; Homatropine; Miosis; Organophosphates; Oxime; Pupillary light reflex; Sarin; TMB-4; VX.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Antidotes / pharmacology*
  • Blinking / drug effects*
  • Chemical Warfare Agents / toxicity*
  • Cholinesterase Inhibitors / toxicity*
  • Cytoprotection
  • Dose-Response Relationship, Drug
  • Eye / drug effects*
  • Eye / enzymology
  • Eye / pathology
  • Eye / physiopathology
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / metabolism
  • Male
  • Miosis / chemically induced
  • Miosis / pathology
  • Miosis / physiopathology
  • Miosis / prevention & control*
  • Muscarinic Antagonists / pharmacology*
  • Organothiophosphorus Compounds / toxicity*
  • Rats, Long-Evans
  • Sarin / toxicity*
  • Time Factors

Substances

  • Antidotes
  • Chemical Warfare Agents
  • Cholinesterase Inhibitors
  • GPI-Linked Proteins
  • Muscarinic Antagonists
  • Organothiophosphorus Compounds
  • VX
  • Sarin
  • Acetylcholinesterase
  • Ache protein, rat