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A. Gore, E. Bloch-Shilderman, I. Egoz, D. Peri, J. Turetz, R. Brandeis; Short-Acting Anti-Cholinergic Agents in Treatment of Topical-Sarin-Induced Miosis and Visual Deficiency in Rats. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1813.
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Eye exposure to the organophosphorus irreversible acetylcholinesterase inhibitor sarin results in long-term miosis and reduction in visual function. Anti-cholinergic drugs, such as atropine, are used topically in order to counter these effects and obtain symptomatic relief. Unfortunately, such compounds attenuate ocular discomfort at the expense of producing mydriasis and partial cycloplegia symptoms, which may worsen visual performance. This study was aimed to test short acting drugs against sarin-induced miosis and visual impairment, which will minimally affect vision.
Male Pigmented Long-Evans rats were topically exposed to sarin (0-10 µg) or propylene glycol, and 20 min later were topically treated with tropicamide, cyclopetolate, atropine or saline. Pupils were illuminated with an infrared spotlight and images were digitally recorded with a computerized infrared-capable video camera, thus measuring pupil width. Miosis was determined as a 50% reduction in pupil width. Pupil width was determined 15 min -72 h following each treatment. Visual function assessment was performed using the "Cued" Morris Water Maze task, 15 min following sarin exposure. In this version, cued navigation involves finding a goal location by approaching a single cue that marks the visible goal. The cue was a circular green rod (5 cm high) attached to the visible escape platform ( 1 cm above the surface of the water).
Rats exposed topically to various sarin doses showed a dose-dependent miosis, which returned to pre-exposure levels within 24-48 h. The threshold dose (ED50) calculated for miosis at 15-120 min following topical sarin exposure was ~0.02 µg. Significant reduction in visual function was seen in animals exposed to 0.2 and 1 µg sarin, opposed to 0.02 µg exposed or control animals. Finally, short-acting anti-cholinergic treatments differentially improved the sarin induced miosis and the resulting impairment in visual performance.
The miotic as well as the visual defects observed following topical sarin exposure are contradicted to various extent by different short-acting anti-cholinergic drugs.
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