Effects of K-115, a Rho-Kinase Inhibitor, on Aqueous Humor Dynamics in Rabbits
2014
AbstractPurpose: To evaluate the topical instillation of K-115, a selective Rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, on intraocular pressure (IOP), ocular distribution, and aqueous humor dynamics in experimental animals.Methods: Kinase inhibition by K-115 was measured by biochemical assay. IOP was monitored using a pneumatonometer in albino rabbits and monkeys after topical instillation of K-115. The ocular distribution of [14C]K-115 was determined by whole-head autoradiography. The aqueous flow rate was determined by fluorophotometry. The total outflow facility and uveoscleral outflow were measured by two-level constant pressure perfusion and perfusion technique using fluorescein isothiocyanate-dextran, respectively.Results: Biochemical assay showed that K-115 had selective and potent inhibitory effects on ROCKs. In rabbits, topical instillation of K-115 significantly reduced IOP in a dose-dependent manner. Maximum IOP reduction was observed 1 h after topical instillation, w...
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