Inhibitory Effect of Pilocarpine on Norepinephrine Release from Electrically Stimulated Iris Dilator Muscles of Rabbits as a Most Possible Mechanism of Pilocarpine-induced Miosis.

Takayanagi, Issei; Kokubu, Noriko; Shiraishi, Koji

doi:10.1540/jsmr.29.55

Cited by 3 publications

(1 citation statement)

References 10 publications

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“…Topical OP ocular exposure leads to a local reduction in cholinesterase (ChE) activity in the iris and ciliary muscle (Dabisch et al, 2005;Lund-Karlsen et al, 1976) with subsequent accumulation of acetylcholine (ACh) (Mattio et al, 1984). Following sublethal exposure, hypercholinergic action upon the iris sphincter muscle results in marked miosis with dim vision, reduction in visual field and difficulty in adapting to both low and high levels of illumination due to desensitization of muscarinic receptors in the iris (Dabisch et al, 2008;Genovese et al, 2008;Lund-Karlsen et al, 1976;Takayanagi et al, 1993). The hypercholinergic action on the ciliary muscle causes an increased tension or even spasm and may lead to blurred vision and myopia accompanied by ocular pain, headaches and nausea (Cannard, 2006;Nohara et al, 1996;Rengstorff, 1985;Smith and Smith, 1980;Yanagisawa et al, 2006).…”

Section: Abbreviationsmentioning

confidence: 99%

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

et al. 2015

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Eye exposure to the extremely toxic organophosphorus sarin results in long-term miosis and visual impairment. As current treatment using atropine or homatropine eye drops may lead to considerable visual side effects, alternative combined treatments of intramuscular (im) oximes (16.8 µmol/kg, im) with atropine (0.5 mg/kg, im) or with the short acting antimuscarinic tropicamide (0.5%; w/v) eye drops were thus evaluated. The combined treatments efficacy following topical exposure to sarin (1 µg) was assessed by measuring pupil width and light reflex using an infra-red based digital photographic system. Results showed that the combined treatment of various oximes with atropine or with topical tropicamide eye drops rapidly reversed the sarin-induced miosis and presented a long-term improvement of 67-98% (oxime+tropicamide) or 84-109% (oxime+atropine) in pupil widening as early as 10-min following treatment. This recovery was shown to persist for at least 8-h following exposure. All combined treatments facilitated the ability of the iris to contract following sarin insult as tested by a light reflex response.Our findings emphasize the high efficacy of im oxime treatment combined with either atropine im or tropicamide eye drops in counteracting sarin-induced ocular insult. Therefore, in a mass casualty scenario the systemic combined treatment may be sufficient to ameliorate sarin-induced ocular insult with no need for additional, topical anticholinergic treatment at least in the initial stage of intoxication. For very mild casualties, who are unlikely to receive im treatment, the combined oxime (im) with topical tropicamide treatment may be sufficient in ameliorating the ocular insult.

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Section: Abbreviationsmentioning

confidence: 99%

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

et al. 2015

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Muscarinic Receptor Agonists and Antagonists: Effects on Ocular Function

Mitchelson

2011

Handbook of Experimental Pharmacology

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Muscarinic agonists act mainly via muscarinic M₃ cholinoceptors to cause contraction of the iris sphincter, ciliary muscle and trabecular meshwork as well as increase outflow facility of aqueous humour. In the iris dilator, the effect of muscarinic agonists is species dependent but is predominantly relaxation via muscarinic M₃ receptors. In the conjunctiva, muscarinic agonists stimulate goblet cell secretion which contributes to the protective tear film. Muscarinic M₂ and M₃ receptors appear mainly involved. In the lens muscarinic agonists act via muscarinic M₁ receptors to produce depolarization and increase [Ca(2+)](i). All five subtypes of muscarinic receptor are present in the retina. In the developing retina, acetylcholine appears to limit purinergic stimulation of retinal development and decrease cell proliferation. In the adult retina acetylcholine and other muscarinic agonists may have complex effects, for example, enhancing light-evoked neuronal firing in transient ON retinal ganglion cells and inhibiting firing in OFF retinal ganglion cells. In the lacrimal gland, muscarinic agonists activate M₃ receptors on secretory globular acinar cells to stimulate tear secretion and also cause contraction of myoepithelial cells. In Sjögren's syndrome, antibodies to the muscarinic M₃ receptor disrupt normal gland function leading to xerophthalmia although the mechanism of action of the antibody is still not clear. Atropine and pirenzepine are useful in limiting the development of myopia in children probably by an action on muscarinic receptors in the sclera, although many other muscarinic receptor antagonists are not effective.

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Optimization of the Ocular Treatment Following Organophosphate Nerve Agent Insult

Egoz

Nili

Grauer

et al. 2017

Toxicological Sciences

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Eye exposure to organophosphate (OP) irreversible acetylcholinesterase inhibitors, results in long-term miosis and impaired visual function. The aim of this study was to find an anticholinergic antidote, which would counteract miosis and visual impairment induced by the nerve agents sarin and VX with minimal untoward side-effects. Rat pupil width and light reflex were evaluated from 15 min up to 2 weeks following topical OP exposure with or without topical ocular treatment of atropine or homatropine or with a combined intramuscular treatment of trimedoxime (TMB-4) and atropine (TA). Visual function following insult and treatment was assessed using a cued Morris water maze task. Topical VX exposure showed a dose-dependent miosis with a significant reduction in visual function similar to the effect seen following sarin exposure. Homatropine (2%; w/v) and atropine (0.1%; w/v) treatment ameliorated both sarin and VX-induced miosis and the resulting visual impairment. TA treatment was sufficient in ameliorating the sarin-induced ocular impairment while an additional ocular treatment with either 0.1% atropine or 2% homatropine was necessary following VX exposure. To conclude the use of 0.1% atropine or 2% homatropine was beneficial in ameliorating the ocular insult following VX or sarin ocular exposure and thus should be considered as universal treatments against this intoxication. The findings also emphasize the necessity of additional ocular treatment to the systemic treatment in visually impaired casualties following VX exposure.

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Inhibitory Effect of Pilocarpine on Norepinephrine Release from Electrically Stimulated Iris Dilator Muscles of Rabbits as a Most Possible Mechanism of Pilocarpine-induced Miosis.

Cited by 3 publications

References 10 publications

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

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

Muscarinic Receptor Agonists and Antagonists: Effects on Ocular Function

Optimization of the Ocular Treatment Following Organophosphate Nerve Agent Insult

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