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Review
. 2018 Mar;62(2):109-126.
doi: 10.1007/s10384-018-0566-9. Epub 2018 Feb 14.

Impact of the clinical use of ROCK inhibitor on the pathogenesis and treatment of glaucoma

Megumi Honjo  1 , Hidenobu Tanihara  2
Affiliations
Review

Impact of the clinical use of ROCK inhibitor on the pathogenesis and treatment of glaucoma

Megumi Honjo et al. Jpn J Ophthalmol. 2018 Mar.

Abstract

Rho-associated protein kinase (ROCK), a ubiquitously expressed signaling messenger and downstream effector of Rho, is activated by several bioactive factors in the aqueous humor (AH). Rho-ROCK signaling regulates a wide spectrum of fundamental cellular events, including cell adhesion, motility, proliferation, differentiation, and apoptosis. Previous studies, including our own, found that ROCK inhibitor lowers intraocular pressure (IOP) via a direct effect on the conventional AH outflow pathway, by regulation of contractile properties, fibrotic activity, and permeability of the trabecular meshwork (TM) and Schlemm's canal (SC) tissues, influencing extracellular matrix (ECM) production. Recently, a novel ROCK inhibitor, ripasudil, has been introduced in Japan. Other ROCK inhibitors are now in clinical trials as new IOP-lowering drugs for glaucoma patients. To date, ripasudil, administered together with other glaucoma medications, has proved safe and efficient in lowering IOP as well as additional effects such as prostaglandin analogs, beta-blockers, and carbonic anhydrase inhibitors, all of which help lower IOP by different mechanisms. In addition, we found that long-term treatment with ripasudil exerted an additional IOP-lowering effect, especially in eyes with high IOP, suggesting that late-onset remodeling of the ECM in glaucomatous eyes may elicit mild and delayed changes in IOP levels. ROCK inhibitors have also shown several additional effects, including increased retinal blood flow, direct protection of neurons against various types of stress, and regulation of wound healing; these benefits may potentially be useful in glaucoma treatment.

Keywords: Conventional outflow; Glaucoma; Intraocular pressure; Rho-associated protein kinase (ROCK) inhibitor; Trabecular meshwork.

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References

    1. Invest Ophthalmol Vis Sci. 1977 Jan;16(1):47-53 - PubMed
    1. Invest Ophthalmol Vis Sci. 2014 Oct 02;55(11):7126-36 - PubMed
    1. Prog Retin Eye Res. 2005 Sep;24(5):612-37 - PubMed
    1. Nat Rev Mol Cell Biol. 2002 May;3(5):349-63 - PubMed
    1. Exp Cell Res. 2006 Nov 1;312(18):3683-92 - PubMed

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