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B. Tian, P.L. Kaufman; Effects of the Rho Kinase Inhibitor Y-27632 and the Phosphatase Inhibitor Calyculin A on Outflow Facility in Monkeys . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3425.
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Purpose: To determine if the Rho kinase inhibitor Y-27632 and the phosphatase inhibitor calyculin A affect outflow facility in monkeys differently and if the latter will inhibit effect of the former on facility. Methods: Total outflow facility was measured by 2-level constant pressure perfusion of the anterior chamber (AC) before and after exchange with different doses of Y-27632 (1, 10 and 100µM) or calyculin A (10, 50 and 100nM), or vehicles, followed by continuous AC infusion of corresponding drug/vehicle solution, in opposite eyes of cynomolgus/rhesus monkeys. The effect of 100µM Y-27632 or 100nM calyculin A vs. vehicle and the effect of 100µM Y-27632 + 100nM calyculin A vs. 100µM Y-27632 alone on outflow facility were also determined in the monkeys pre-treated with 10µl of 1% topical atropine in both eyes 1 hr before perfusion. Results: Both Y-27632 and calyculin A dose-dependently increased outflow facility in monkeys during 90-min post-drug perfusion. After adjustment for baseline and contralateral control eye washout, the increase in outflow facility caused by 1, 10 or 100µM Y-27632 was 2±19% (n=4, P>0.9), 55±19% (n=8, P<0.05) or 206±30% (n=5, P<0.005), and the increase in facility caused by10, 50 or 100nM calyculin A was 28±35% (n=6, P<0.5), 37±10% (n=5, P<0.025) or 189±57% (n=6, P<0.025). Pre-treatment with 1% topical atropine partially inhibited the effect of 100nM calyculin A, but not 100µM Y-27632, on outflow facility. 100nM calyculin A had no effect on the facility increase caused by Y -27632 initially, but gradually and partially inhibited the Y-27632-induced facility increase by up to 32±12% (n=6, P<0.05) during the 4th 30-min period of 2-hr post-drug perfusion. Conclusions:The Rho kinase inhibitor Y-27632 increases outflow facility in monkeys presumably by inhibiting cellular contractility in the TM. The phosphatase inhibitor calyculin A increases outflow facility by complicated mechanisms perhaps including drug-induced ciliary muscle contraction and cytoskeleton changes in TM cells. The partial inhibitory effect of calyculin A on Y-27632 may reflect the former partially inhibiting the latter's relaxation of cells in the TM. Further studies are needed.
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