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Japanese Journal of Ophthalmology

, Volume 62, Issue 2, pp 109–126 | Cite as

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

Forefront Review Section Organizer: Makoto Aihara, MD, PhD
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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

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

Notes

Acknowledgements

This work was supported by the Japan Society for the Promotion of Science (JSPS) Grant Number 15K10854 (MH).

Conflicts of interest

M. Honjo, Analysis Support (Kowa); H. Tanihara, Analysis Support (Kowa).

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Copyright information

© Japanese Ophthalmological Society 2018

Authors and Affiliations

  1. 1.Department of Ophthalmology, Graduate School of MedicineThe University of TokyoTokyoJapan
  2. 2.Department of Ophthalmology, Faculty of Life SciencesKumamoto UniversityKumamotoJapan

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