Rho-associated Kinase Inhibitors for the Treatment of Ocular Diseases
Journal Title: Ophthalmology and Vision Science - Year 2016, Vol 1, Issue 1
Abstract
The Rho family consists of a series of small G-proteins, including RhoA, RhoB, and RhoC. When bounded to guanosine triphosphate, Rho molecules activate their effectormolecule,Rho-associated kinase (ROCK). A Rho-ROCK signal is a regulator of factors such calciumindependent smooth muscle contraction, cell adhesion and motility, as well as of actin cytoskeleton [1]. In September 2014, a ROCK inhibitor, ripasudil,was approved in Japan for the treatment of glaucoma and ocular hypertension as the first anti-glaucoma agent of this category in the world.In this Editorial, I describe the unique mechanisms by which ROCK inhibitors lower intraocular pressure (IOP), as well as their other actions. It was found in Japan that several kinds of ROCK inhibitors, including Y-27632 and HA1077 (fasudil), reduce IOP by increasing conventional outflow through the Schlemm canal. Honjo., et al. Reported that administration of the ROCK inhibitors caused a reduction in IOP and an increase in the outflow facility in rabbits. Their in vitro experiments suggested that the IOP-lowering effects of the ROCK inhibitors might be related to the altered cellular behavior of trabecular meshwork cells and relaxation of ciliary muscle contraction [2,3]. Ripasudil, a selective ROCK inhibitor, has recently been approved for human use after undergoing a series of clinical trials, and was found to have additive effect when combined with timolol or latanoprost [4-6]. It is noteworthy that ripasudil is now the only anti-glaucoma agent in clinical use that lowers IOP by modulating the conventional aqueous outflow pathway [7].
Authors and Affiliations
Tetsuya Sugiyama
Keywords
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Rho-associated Kinase Inhibitors for the Treatment of Ocular Diseases
The Rho family consists of a series of small G-proteins, including RhoA, RhoB, and RhoC. When bounded to guanosine triphosphate, Rho molecules activate their effectormolecule,Rho-associated kinase (ROCK). A Rho-ROCK sign...