[PDF] Effects of topical administration of y-39983, a selective rho-associated protein kinase inhibitor, on ocular tissues in rabbits and monkeys. | Semantic Scholar (2024)

Y-39983 may be a candidate drug not only for lowering of IOP but also for increasing of blood flow in ONH in the treatment of glaucoma, although improvements of formulation or route of administration are needed in order to reach an effective concentration in retina.

Results indicated that K-115 ophthalmic solution, a selective and potent ROCK inhibitor, is a novel and potent antiglaucoma agent.

The magnitude of IOP reduction is significant as demonstrated with comparative pharmacology using agents that lower IOP in humans, and support the ROCK pathway as a therapeutic target for treating ocular hypertension.

It is concluded that Y-27632 and Y-39983 relaxed isolated rabbit ciliary artery segments in vitro, and the mechanism of relaxation was not dependent on endothelial-derived factors such as nitric oxide (NO) or prostacyclin, nor was it dependent on changes in intracellular Ca2+ concentration.

AMA0076 is a locally acting ROCK inhibitor that is able to induce altered cellular behavior of HTM cells that effectively reduces IOP in ocular normotensive and acute hypertensive rabbits without causing distinct hyperemia.

Topical administration of H-1152P potently decreased rabbit normotensive IOPs in a dose-dependent manner, and the duration of the IOP lowering was also elongated in a doses dependent manner, suggesting that H- 1152P could be a candidate for the next generation of glaucoma therapy.

I-E-212 is a novel and highly specific ROCK2 inhibitor with the ability to lower IOP in animal models and has favorable pharmaco*kinetic and ocular tolerability profiles with only minimal conjunctival hyperemia.

Y-27632 had profound effects on activities of HTFs and was effective in preventing fibroproliferation and scar formation in a rabbit model of glaucoma surgery and a ROCK inhibitor may be an effective anti-scarring agent after glAUcoma filtering surgery.

Y-27632 increased the permeability of the SCE-cell monolayer in association with disruption of the tight junction, F-actin depolymerization, and changes in various cell functions, including calcium transfer.

It is anticipated that care in order and timing of ROCK inhibitor administration will be warranted for those patients who may be on a multiple topical drug regimen for primary open-angle glaucoma.

...

...

In vitro experiments suggest that the IOP-lowering effects of Y-27632 may be related to the altered cellular behavior of TM cells and relaxation of CM contraction, and suggest that ROCK inhibitors may have great potential to be developed for treatment of glaucoma and other ocular diseases.

The results of in vitro experiments suggest that the IOP-lowering effects of HA1077 may be related to the altered cellular behavior of TM cells and relaxation of CM contraction, and have the potential to be developed into a treatment modality for glaucoma.

The ROCK inhibitor reduced intraocular pressure in rabbits by topical instillation and relaxed the excised ciliary muscle which was previously constricted by carbachol suggesting that the inhibitor acts to increase the uveoscleral outflow.

Five percent H-7 increases outflow facility and decreases IOP, but does not affect corneal thickness, in monkeys with laser-induced unilateral glaucoma and multiple doses induce greater reduction of IOP than a single dose.

H-7 increases outflow facility in monkeys, probably by inhibiting cell contractility, cytoskeletal support, and cell-cell adhesions in the trabecular meshwork.

Unoprostone lowers the IOP by affecting aqueous outflow pathways, primarily the pressure-dependent conventional pathway and the secondary uveoscleral outflow pathway in rabbits.

Results indicate that both rho p21 and rho GDI, but neither rac p21 nor ras p21, are involved in the HGF-induced cell motility.

These studies demonstrate that LPA and S1P, the physiological agonists of Edg receptors, decrease outflow facility in perfused porcine eyes in association with increased MLC phosphorylation and Rho guanosine triphosphatase (GTPase) activation.

...

...