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C.B. Toris, S. Fan, M.A. McLaughlin; The Rho–Kinase Inhibitor, AL–38565A, Reduces Aqueous Flow in Monkeys . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2945.
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© ARVO (1962-2015); The Authors (2016-present)
The rho kinase inhibitor AL–37599 (Y–27632) in monkeys increases uveoscleral outflow, outflow facility and aqueous flow (McLaughlin, ARVO 2004 abstract#3534). The purpose of the current study was to determine whether another rho kinase inhibitor, AL–38565A (HMN–1152, H), works by the same mechanism to lower intraocular pressure (IOP).
Eleven cynomolgus monkeys of either sex were included in the study. Seven had unilateral laser treatment to the trabecular meshwork of the right eye. Four were ocular normotensive. Measurements were made twice, once on baseline day and once after two doses of H treatment to both eyes. Assessments included anterior chamber volume by slit–lamp pachymetry, IOP by pneumatonometry, aqueous flow (AF) and outflow facility (C) by fluorophotometry, and uveoscleral outflow by mathematical calculation and by intracameral infusion of FITC dextran tracer. Animals were anesthetized with isoflurane gas for the tracer studies and ketamine for all other measurements. Comparisons were made using paired two–tailed t–tests.
In normotensive eyes, H reduced IOP (p=0.005) by 17% at 3 hr after the second dose. Compared to baseline, there was a significant (p<0.001) 30% decrease in AF and no change in C or uveoscleral outflow. In hypertensive eyes, H did not significantly reduce IOP (p=0.09) at any time measured between baseline and treatment day. Compared to baseline, there was a significant (p=0.03) 26% decrease in AF and no change in C or uveoscleral outflow. The tracer studies found no increase in uveoscleral outflow when comparing treated with contralateral untreated normotensive eyes (n=4) or when comparing treated hypertensive eyes (n=7) to untreated hypertensive eyes from a previous study (Toris, J Ocular Pharm Ther 16:19–27, 2000; n=15).
AL–38565A (H) significantly reduced IOP and aqueous flow in normotensive eyes of ketamine–sedated monkeys. The IOP lowering mechanism of action of this rho kinase inhibitor is apparently different from that of AL–37599 (Y–27632). It may be that reduction in aqueous flow cannot be generalized to all drugs of this class.
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