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

Gore, Ariel; Lazar, Shlomi; Yacov, Guy; Gez, Rellie; Rabinowitz, Ishai; Nili, Uri; Egoz, Inbal; Kadar, Tamar

doi:10.1016/j.toxlet.2019.08.002

Cited by 3 publications

(1 citation statement)

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“…Of note are several publications addressing visual and ocular effects, impaired learning and memory, as well as histopathology in the brain in rat models of acute sarin exposure. Direct exposure of the eye to sarin was reported to cause dose-dependent miosis, reduced visual function, and ocular surface histopathological lesions that persisted days to weeks post-exposure (Egoz et al 2017;Gore et al 2019). Acute sarin intoxication also caused significantly impaired performance of rats in the Morris water maze test of learning and memory that persisted for up to 3 months post-exposure (Lewine et al 2018;Lumley et al 2019).…”

Section: What Is the Biological Plausibility Of Long-term Neurological Effects?mentioning

confidence: 99%

A national toxicology program systematic review of the evidence for long-term effects after acute exposure to sarin nerve agent

Jett

Sibrizzi

Blain

et al. 2020

Critical Reviews in Toxicology

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Sarin is a highly toxic nerve agent that was developed for chemical warfare during World War II and is used in present conflicts. Immediate effects of acute sarin exposure are established; however, whether effects persist after initial signs have subsided is debated. The National Toxicology Program (NTP) conducted a systematic review to evaluate the evidence for long-term neurological effects following acute (<24 hour) exposure to sarin. The literature search and screening process identified 32 data sets within the 34 human studies and 47 data sets within the 51 animal studies (from 6837 potentially relevant references) that met the objective and the inclusion criteria. Four main health effect categories of neurological response were identified as having sufficient data to reach hazard conclusions: (1) cholinesterase levels; (2) visual and ocular effects; (3) effects on learning, memory, and intelligence; and (4) morphology and histopathology in nervous system tissues. NTP concluded that acute sarin exposure is known to be a neurological hazard to humans in the period following exposure up to 7 days and suspected to be a hazard week to years after exposure, given a lower level of evidence in later time periods. Effects included reduced cholinesterase, visual and ocular effects, impaired learning and memory, and altered nervous system morphology. Further mechanistic, targeted animal studies, translational research, and rapid research responses after human exposures may reduce uncertainties on long-term consequences of sarin.

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Section: What Is the Biological Plausibility Of Long-term Neurological Effects?mentioning

confidence: 99%

A national toxicology program systematic review of the evidence for long-term effects after acute exposure to sarin nerve agent

Jett

Sibrizzi

Blain

et al. 2020

Critical Reviews in Toxicology

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Rapid formation of a shelter-in-place using a combination of vortex flow and chemical oxidation for indoor environments containing neurotoxic gases

Gao

Zhang

et al. 2021

Building and Environment

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Broad Spectrum Treatment for Ocular Insult Induced by Organophosphate Chemical Warfare Agents

Gore

2020

Toxicological Sciences

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Warfare organophosphates (OP) nerve agents constitute one of the prime threats to mankind on the battlefield and in the scenario of civilian terror. Exposure to OP nerve agents dose-dependently result in incapacitation. They affect multiple organs, but the eye is one of the first and most frequently affected. Ocular OP insult may result in long-term miosis, impaired visual function and ocular pain thus inducing functional incapacitation. The currently recommended military medical doctrine of using 1% atropine eye drops is far from being the optimal treatment. Although effective in reducing ocular pain and the miotic response, this treatment induces long-term mydriasis and cycloplegia promoting photophobia and restricted accommodation, which may result in further impairment in visual function. An optimal treatment must ameliorate the long-term ocular insult enabling rapid return of normal visual function, while avoiding the induction of mydriasis and cycloplegia side effects, which could possibly worsen the visual performance. Optimal treatment should also keep effects of misuse to a minimum. Work done in recent years examined treatments with various anti-cholinergic drugs alone or used in combination with oxime treatments and may offer improved efficacy in ameliorating the ocular insult. This review is a summary of the applied research in animals and will discuss clinical implications and possible alterations in treatment protocols following OP exposure. Taken together the data points towards the use of topical low concentrations of potent anticholinergic ophthalmic drops such as atropine or homatropine, which rapidly ameliorate the long term OP induced ocular insult.

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

Cited by 3 publications

References 48 publications

A national toxicology program systematic review of the evidence for long-term effects after acute exposure to sarin nerve agent

A national toxicology program systematic review of the evidence for long-term effects after acute exposure to sarin nerve agent

Rapid formation of a shelter-in-place using a combination of vortex flow and chemical oxidation for indoor environments containing neurotoxic gases

Broad Spectrum Treatment for Ocular Insult Induced by Organophosphate Chemical Warfare Agents

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