Correlations Between Acetylcholinesterase Activity in Guinea‐Pig Iris and Pupillary Function: A Biochemical and Pupillographic Study

Abstract

Acetylcholinesterase (AChE) in guinea pig iris was inhibited by methylisocyclopentylfluorophosphate (soman) administered topically or parenterally, and enzyme activity was correlated to pupillary diameter by infrared pupillography. After a single topical soman instillation into the conjunctival sac there was an almost linear relationship between the reduction in AChE activity and pupillary diameter. Topical administration of soman at 24-h intervals in doses capable of almost complete inhibition of AChE in iris was accompanied by a reduced miotic effect of this drug. This was indicated by a reduced rate of the soman-induced pupillary constriction, a less pronounced reduction in pupillary diameter, and a more rapid return of the pupillary diameter to normal size. The change in pupillary diameter occurred after three daily administrations and remained constant during 31 days of treatment. These observations were seen irrespective of inhibition of blood AChE. The decrease in response to repeated administration could not be explained by a reduced inhibitory effect of soman on AChE, by a more rapid de novo synthesis of AChE, or by a change in the number of the muscarinic receptors as determined by quinuclidinyl benzilate binding. When soman or DFP was administered subcutaneously in high doses a severe AChE inhibition was obtained in iris without any concomitant miosis.

Low‐level exposure of guinea pigs and marmosets to sarin vapour in air: lowest‐observable‐adverse‐effect level (LOAEL) for miosis

“…Whether a relationship exists between the AChE activity in the iris and the degree of miosis seems to depend of the route of poisoning. Only in the case of local poisoning is the degree of miosis linearly correlated with the degree of AChE activity in the iris (Soli et al, 1980). In a similar way it may be explained that pretreatment with pyridostigmine does not alter the LOAEL for miosis.…”

“…The relationship between AChE activity in guinea-pig iris and blood, and pupillary function after local or systemic administration of soman, was investigated by Soli et al (1980). When soman (or DEP) was administered subcutaneously in high doses, a severe AChE inhibition was obtained in blood and iris without any concomitant miosis.…”

Development of Miotic Cross-Tolerance Between Pyridostigmine and Sarin Vapor

“…As mentioned previously, multiple exposures to CWAs, including GB vapor, result in miotic tolerance. 3,4,17 However, it is unknown whether preexposure to a different cholinesterase inhibitor, such as PB, would result in tolerance to the miotic effect of GB vapor. If this cross-tolerance occurs, then the utility of miosis as a biomarker for nerve agent exposure may be decreased in soldiers taking PB prophylactically.…”

“…16 Tolerance to the miotic effect of cholinergic agonists has also been reported previously and is likely caused by desensitization of muscarinic receptors on the pupillary sphincter muscle. 3,4,17 Based on the results of these previous studies, it was hypothesized that multiple injections of PB would result in tolerance to the miotic effect of PB exposure. In this study, animals exposed twice-daily to PB developed tolerance to the miotic effect of PB administration on the 3rd d of administration, confirming this hypothesis.…”

Ocular Toxicity of Chemical Warfare Agents

“…This is corroborated by multiple findings. First, it was shown that nerve agentinduced miosis is inversely proportional to AChE activity in the iris (Soli et al, 1980). Second, pretreatment with the muscarinic receptor antagonist atropine prevents the miotic response (Dabisch et al, 2005).…”