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A.B. Kharlamb, D.F. Woodward, R.M. Burk, M. Holoboski, M. Posner; Ciliary Muscle Relaxation Does Not Explain the Profound Ocular Hypotension Produced by a Selective Prostanoid EP4 Receptor Agonist 3,7–Dithia PGE1 in Monkeys . Invest. Ophthalmol. Vis. Sci. 2006;47(13):413.
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The prostanoid EP4 receptor is unique in that it mediates profound ocular hypotension in primates by a mechanism that does not involve uveoscleral outflow. The ocular hypotensive response to the selective EP4 receptor agonist 3,7–dithia PGE1 is partly explained by increased conventional outflow but there remains an IOP component for which no satisfactory mechanistic explanation has emerged. The purpose of these studies was to investigate ciliary smooth muscle relaxation as a contributory mechanism to the profound ocular hypotension produced by the EP4 agonist 3,7–dithia PGE1.
Human and cynomolgus ciliary smooth muscle specimens were surgically excised from enucleated eyes and set up as either radial or longitudinal preparations in 15ml organ baths containing Kreb’s buffer and gassed with 95% O2/5% CO2.. Each ciliary muscle preparation was pre–contracted to approximately 50% maximum by carbachol to enable any relaxant responses to 3,7–dithia PGE1, prostaglandin E2(PGE2), or atropine to be readily occur. Responses were recorded isometrically on a Grass polygraph.
3,7–dithia PGE1 exerted no meaningful relaxant effects on either radial or longitudinal human ciliary smooth muscle preparations. No response was apparent until a 10–5M concentration of 3,7–dithia PGE1 was achieved, which is far in excess of that necessary to fully activate EP4 receptors. PGE2 was more active and the antagonist atropine completely reversed carbachol induced contraction, thereby indicating the viability of the tissue preparations. Virtually identical results were obtained from studies in a limited number of monkey radial and longitudinal ciliary muscle preparations.
EP4 receptor stimulation does not cause relaxation of primate ciliary muscle. It follows that ciliary muscle relaxation is not a contributory factor to the increase in aqueous humor outflow produced by the EP4 agonist 3,7–dithia PGE1 in primates.
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