Efficacy assessment of a combined anticholinergic and oxime treatment against topical sarin‐induced miosis and visual impairment in rats

Abstract

BACKGROUND AND PURPOSEEye exposure to the organophosphorus (OP) irreversible cholinesterase inhibitor sarin results in long-term miosis and impaired visual function. We have previously shown that tropicamide is better at ameliorating this insult than topical atropine or cyclopentolate. However, to minimize side effects associated with repeated tropicamide applications and high treatment doses, we evaluated the effects of oximes (ChE re-activators) alone and combined with tropicamide at ameliorating OP-induced ocular impairments. EXPERIMENTAL APPROACHRats were topically exposed to sarin, followed by topical treatment with various oximes alone or in combination with tropicamide. Pupil width and light reflex were measured by an infrared-based digital photograph system, while visual performance was assessed by employing the cueing version of the Morris water maze (MWM).

Eyeing up the Future of the Pupillary Light Reflex in Neurodiagnostics

“…In support of this, oximes, which reactivate acetylcholinesterase, had no effect on sarin-induced miosis in animal models. Moreover, tropicamide—a muscarinic receptor antagonist that competes with ACh for binding sites, preventing receptor desensitisation—rapidly increased pupil size and restored PLR [ 143 ]. However, organophosphates inactivate cholinesterases at both muscarinic and nicotinic receptor sites and paradoxical pupil dilation or mydriasis may occur in certain circumstances due to dominant nicotinic effects at the pre-ganglionic fibres of the sympathetic nervous system, resulting in increased innervation of the dilator muscle [ 144 , 145 ].…”

Synergism Between Anticholinergic and Oxime Treatments Against Sarin-Induced Ocular Insult in Rats

“…We have previously reported that a topical combined treatment may reduce the need of repeated anticholinergic treatments (Gore et al, 2014). As oximes are not approved for ocular use in humans, a combined topical treatment is as yet unavailable.…”

“…In order to minimize repeated treatments or the misuse side effects of mydriasis and cycloplegia (Bartlett et al, 2008), we hypothesized that a combined treatment of im oxime and topical tropicamide may be beneficial in counteracting ocular symptoms, as tropicamide will rapidly widen the iris and reduce ciliary spasm while the oxime will reactivate ocular ChE, preventing recurrence of ocular toxic symptoms as has been demonstrated previously using topical combined treatments (Gore et al, 2014). In addition, this combined treatment may enable the reduction of tropicamide dose, reducing the intensity and duration of mydriasis and partial cycloplegia side effects in cases of misuse.…”