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Japanese Journal of Ophthalmology
Erschienen in: Japanese Journal of Ophthalmology 2/2018

14.02.2018 | Forefront Review

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

verfasst von: Megumi Honjo, Hidenobu Tanihara

Erschienen in: Japanese Journal of Ophthalmology | Ausgabe 2/2018

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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.
Literatur
1.
Iwase A, Suzuki Y, Araie M, Yamamoto T, Abe H, Shirato S, et al. The prevalence of primary open-angle glaucoma in Japanese: the Tajimi study. Ophthalmology. 2004;111:1641–8.PubMed
2.
Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014;121:2081–90.PubMedCrossRef
3.
4.
5.
Caprioli J, Coleman AL. Blood pressure, perfusion pressure, and glaucoma. Am J Ophthalmol. 2010;149:704–12.PubMedCrossRef
6.
7.
8.
9.
10.
Gabelt BAT, Kaufman PL. Changes in aqueous humor dynamics with age and glaucoma. Prog Retin Eye Res. 2005;24:612–37.PubMedCrossRef
11.
12.
Mäepea O, Bill A. Pressures in the juxtacanalicular tissue and Schlemm’s canal in monkeys. Exp Eye Res. 1992;54:879–83.PubMedCrossRef
13.
Honjo M, Tanihara H, Inatani M, Kido N, Sawamura T, Yue BY, et al. Effects of Rho-associated protein kinase inhibitor Y-27632 on intraocular pressure and outflow facility. Invest Ophthalmol Vis Sci. 2001;42:137–44.PubMed
14.
Kaneko Y, Ohta M, Inoue T, Mizuno K, Isobe T, Tanabe S, et al. Effects of K-115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm’s canal endothelial cells. Sci Rep. 2016;6:19640.PubMedPubMedCentralCrossRef
15.
Fujimoto T, Inoue T, Kameda T, Kasaoka N, Inoue-Mochita M, Tsuboi N, et al. Involvement of RhoA/Rho-associated kinase signal transduction pathway in dexamethasone-induced alterations in aqueous outflow. Invest Ophthalmol Vis Sci. 2012;53:7097–108.PubMedCrossRef
16.
Kameda T, Inoue T, Inatani M, Fujimoto T, Honjo M, Kasaoka N, et al. The effect of Rho-associated protein kinase inhibitor on monkey Schlemm’s canal endothelial cells. Invest Ophthalmol Vis Sci. 2012;53:3092–103.PubMedCrossRef
17.
Honjo M, Tanihara H, Kameda T, Kawaji T, Yoshimura N, Araie M. Potential role of Rho-associated protein kinase inhibitor Y-27632 in glaucoma filtration surgery. Invest Ophthalmol Vis Sci. 2007;48:5549–57.PubMedCrossRef
18.
Inoue T, Tanihara H. Rho-associated kinase inhibitors: a novel glaucoma therapy. Prog Retin Eye Res. 2013;37:1–12.PubMedCrossRef
19.
Clark AF, Wordinger RJ. The role of steroids in outflow resistance. Exp Eye Res. 2009;88:752–9.PubMedCrossRef
20.
21.
Stamer WD, Read AT, Sumida GM, Ethier CR. Sphingosine-1-phosphate effects on the inner wall of Schlemm’s canal and outflow facility in perfused human eyes. Exp Eye Res. 2009;89:980–8.PubMedPubMedCentralCrossRef
22.
Shepard AR, Millar JC, Pang IH, Jacobson N, Wang WH, Clark AF. Adenoviral gene transfer of active human transforming growth factor-{beta}2 elevates intraocular pressure and reduces outflow facility in rodent eyes. Invest Ophthalmol Vis Sci. 2010;51:2067–76.PubMedCrossRef
23.
Keller KE, Aga M, Bradley JM, Kelley MJ, Acott TS. Extracellular matrix turnover and outflow resistance. Exp Eye Res. 2009;88:676–82.PubMedCrossRef
24.
Gottanka J, Chan D, Eichhorn M, Lutjen-Drecoll E, Ethier CR. Effects of TGF-beta2 in perfused human eyes. Invest Ophthalmol Vis Sci. 2004;45:153–8.PubMedCrossRef
25.
Wiederholt M, Thieme H, Stumpff F. The regulation of trabecular meshwork and ciliary muscle contractility. Prog Retin Eye Res. 2000;19:271–95.PubMedCrossRef
26.
Iyer P, Lalane R 3rd, Morris C, Challa P, Vann R, Rao PV. Autotaxin-lysophosphatidic acid axis is a novel molecular target for lowering intraocular pressure. PLoS One. 2012;7:e42627.PubMedPubMedCentralCrossRef
27.
Wang RF, Williamson JE, Kopczynski C, Serle JB. Effect of 0.04% AR-13324, a ROCK, and norepinephrine transporter inhibitor, on aqueous humor dynamics in normotensive monkey eyes. J Glaucoma. 2015;24:51–4.PubMedCrossRef
28.
29.
30.
Cherfils J, Zeghouf M. Regulation of small GTPases by GEFs, GAPs, and GDIs. Physiol Rev. 2013;93:269–309.PubMedCrossRef
31.
Shimokawa H, Sunamura S, Satoh K. RhoA/rho-kinase in the cardiovascular system. Circ Res. 2016;118:352–66.PubMedCrossRef
32.
Ishizaki T, Maekawa M, Fujisawa K, Okawa K, Iwamatsu A, Fujita A, et al. The small GTP-binding protein Rho binds to and activates a 160 kDa Ser/Thr protein kinase homologous to myotonic dystrophy kinase. EMBO J. 1996;15:1885–93.PubMedPubMedCentral
33.
Thumkeo D, Watanabe S, Narumiya S. Physiological roles of Rho and Rho effectors in mammals. Eur J Cell Biol. 2013;92:303–15.PubMedCrossRef
34.
Somlyo AP, Somlyo AV. Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev. 2003;83:1325–58.PubMedCrossRef
35.
Maekawa M, Ishizaki T, Boku S, Watanabe N, Fujita A, Iwamatsu A, et al. Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase. Science. 1999;285:895–8.PubMedCrossRef
36.
Amano M, Kaneko T, Maeda A, Nakayama M, Ito M, Yamauchi T, et al. Identification of Tau and MAP2 as novel substrates of Rho-kinase and myosin phosphatase. J Neurochem. 2003;87:780–90.PubMedCrossRef
37.
38.
Fukata Y, Amano M, Kaibuchi K. Rho–Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. Trends Pharmacol Sci. 2001;22:32–9.PubMedCrossRef
39.
Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T, et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997;389:990–4.PubMedCrossRef
40.
Nakagawa O, Fujisawa K, Ishizaki T, Saito Y, Nakao K, Narumiya S. ROCK-I and ROCK-II, two isoforms of Rho-associated coiled-coil forming protein serine/threonine kinase in mice. FEBS Lett. 1996;392:189–93.PubMedCrossRef
41.
42.
Fukiage C, Mizutani K, Kawamoto Y, Azuma M, Shearer TR. Involvement of phosphorylation of myosin phosphatase by ROCK in trabecular meshwork and ciliary muscle contraction. Biochem Biophys Res Commun. 2001;288:296–300.PubMedCrossRef
43.
Whitlock NA, Harrison B, Mixon T, Yu XQ, Wilson A, Gerhardt B, et al. Decreased intraocular pressure in mice following either pharmacological or genetic inhibition of ROCK. J Ocul Pharmacol Ther. 2009;25:187–94.PubMedCrossRef
44.
Amin E, Dubey BN, Zhang SC, Gremer L, Dvorsky R, Moll JM, et al. Rho-kinase: regulation, (dys)function, and inhibition. Biol Chem. 2013;394:1399–410.PubMedPubMedCentralCrossRef
45.
Knipe RS, Tager AM, Liao JK. The Rho kinases: critical mediators of multiple profibrotic processes and rational targets for new therapies for pulmonary fibrosis. Pharmacol Rev. 2015;67:103–17.PubMedPubMedCentralCrossRef
46.
Loirand G. Rho Kinases in Health and Disease: From Basic Science to Translational Research. Pharmacol Rev. 2015;67:1074–95.PubMedCrossRef
47.
48.
Epstein DL, Rowlette LL, Roberts BC. Acto-myosin drug effects and aqueous outflow function. Invest Ophthalmol Vis Sci. 1999;40:74–81.PubMed
49.
Erickson-Lamy K, Schroeder A, Epstein DL. Ethacrynic acid induces reversible shape and cytoskeletal changes in cultured cells. Invest Ophthalmol Vis Sci. 1992;33:2631–40.PubMed
50.
Kaufman PL, Barany EH. Cytochalasin B reversibly increases outflow facility in the eye of the cynomolgus monkey. Invest Ophthalmol Vis Sci. 1977;16:47–53.PubMed
51.
Peterson JA, Tian B, Bershadsky AD, Volberg T, Gangnon RE, Spector I, et al. Latrunculin-A increases outflow facility in the monkey. Invest Ophthalmol Vis Sci. 1999;40:931–41.PubMed
52.
Tian B, Geiger B, Epstein DL, Kaufman PL. Cytoskeletal involvement in the regulation of aqueous humor outflow. Invest Ophthalmol Vis Sci. 2000;41:619–23.PubMed
53.
Tian B, Kaufman PL, Volberg T, Gabelt BT, Geiger B. H-7 disrupts the actin cytoskeleton and increases outflow facility. Arch Ophthalmol. 1998;116:633–43.PubMedCrossRef
54.
Waki M, Yoshida Y, Oka T, Azuma M. Reduction of intraocular pressure by topical administration of an inhibitor of the Rho-associated protein kinase. Curr Eye Res. 2001;22:470–4.PubMedCrossRef
55.
Rao PV, Deng PF, Kumar J, Epstein DL. Modulation of aqueous humor outflow facility by the Rho kinase-specific inhibitor Y-27632. Invest Ophthalmol Vis Sci. 2001;42:1029–37.PubMed
56.
Tokushige H, Waki M, Takayama Y, Tanihara H. Effects of Y-39983, a selective Rho-associated protein kinase inhibitor, on blood flow in optic nerve head in rabbits and axonal regeneration of retinal ganglion cells in rats. Curr Eye Res. 2011;36:964–70.PubMedCrossRef
57.
Honjo M, Inatani M, Kido N, Sawamura T, Yue BYJT, Honda Y, et al. A myosin light chain kinase inhibitor, ML-9, lowers the intraocular pressure in rabbit eyes. Exp Eye Res. 2002;75:135–42.PubMedCrossRef
58.
Nishio M, Fukunaga T, Sugimoto M, Ikesugi K, Sumi K, Hidaka H, et al. The effect of the H-1152P, a potent Rho-associated coiled coil-formed protein kinase inhibitor, in rabbit normal and ocular hypertensive eyes. Curr Eye Res. 2009;34:282–6.PubMedCrossRef
59.
Feng Y, Yin Y, Weiser A, Griffin E, Cameron MD, Lin L, et al. Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. J Med Chem. 2008;51:6642–5.PubMedPubMedCentralCrossRef
60.
Pakravan M, Beni AN, Ghahari E, Varshochian R, Yazdani S, Esfandiari H, et al. The ocular hypotensive efficacy of topical fasudil, a Rho-associated protein kinase inhibitor, in patients with end-stage glaucoma. Am J Ther. 2017;24:e676–80.PubMedCrossRef
61.
de Kater AW, Shahsafaei A, Epstein DL. Localization of smooth muscle and nonmuscle actin isoforms in the human aqueous outflow pathway. Invest Ophthalmol Vis Sci. 1992;33:424–9.PubMed
62.
Rao PV, Deng P, Sasaki Y, Epstein DL. Regulation of myosin light chain phosphorylation in the trabecular meshwork: role in aqueous humour outflow facility. Exp Eye Res. 2005;80:197–206.PubMedCrossRef
63.
Epstein DL, Freddo TF, Bassett-Chu S, Chung M, Karageuzian L. Influence of ethacrynic acid on outflow facility in the monkey and calf eye. Invest Ophthalmol Vis Sci. 1987;28:2067–75.PubMed
64.
Ethier CR, Read AT, Chan DW. Effects of latrunculin-B on outflow facility and trabecular meshwork structure in human eyes. Invest Ophthalmol Vis Sci. 2006;47:1991–8.PubMedCrossRef
65.
Inoue T, Pattabiraman PP, Epstein DL, Vasantha Rao P. Effects of chemical inhibition of N-WASP, a critical regulator of actin polymerization on aqueous humor outflow through the conventional pathway. Exp Eye Res. 2010;90:360–7.PubMedCrossRef
66.
Bill A, Svedbergh B. Scanning electron microscopic studies of the trabecular meshwork and the canal of Schlemm—an attempt to localize the main resistance to outflow of aqueous humor in man. Acta Ophthalmol. 1972;50:295–320.CrossRef
67.
Stamer WD, Braakman ST, Zhou EH, Ethier CR, Fredberg JJ, Overby DR, et al. Biomechanics of Schlemm’s canal endothelium and intraocular pressure reduction. Prog Retin Eye Res. 2015;44:86–98.PubMedCrossRef
68.
Kumar J, Epstein DL. Rho GTPase-mediated cytoskeletal organization in Schlemm’s canal cells play a critical role in the regulation of aqueous humor outflow facility. J Cell Biochem. 2011;112:600–6.PubMedCrossRef
69.
Gong H, Jin X. Potts model partition functions on two families of fractal lattices. Physica A. 2014;414:143–53.CrossRef
70.
Pattabiraman PP, Maddala R, Rao PV. Regulation of plasticity and fibrogenic activity of trabecular meshwork cells by Rho GTPase signaling. J Cell Physiol. 2014;229:927–42.PubMedPubMedCentralCrossRef
71.
Zhang M, Maddala R, Rao PV. Novel molecular insights into RhoA GTPase-induced resistance to aqueous humor outflow through the trabecular meshwork. Am J Physiol. 2008;295:C1057–70.CrossRef
72.
Vittitow JL, Garg R, Rowlette LL, Epstein DL, O’Brien ET, Borras T. Gene transfer of dominant-negative RhoA increases outflow facility in perfused human anterior segment cultures. Mol Vis. 2002;8:32–44.PubMed
73.
Rao PV, Deng P, Maddala R, Epstein DL, Li CY, Shimokawa H. Expression of dominant negative Rho-binding domain of Rho-kinase in organ cultured human eye anterior segments increases aqueous humor outflow. Mol Vis. 2005;11:288–97.PubMed
74.
Borras T, Buie LK, Spiga MG, Carabana J. Prevention of nocturnal elevation of intraocular pressure by gene transfer of dominant-negative RhoA in rats. JAMA Ophthalmol. 2015;133:182–90.PubMedPubMedCentralCrossRef
75.
Pattabiraman PP, Rinkoski T, Poeschla E, Proia A, Challa P, Rao PV. RhoA GTPase-induced ocular hypertension in a rodent model is associated with increased fibrogenic activity in the trabecular meshwork. Am J Pathol. 2015;185:496–512.PubMedPubMedCentralCrossRef
76.
77.
78.
Kaufman PL, Barany EH. Loss of acute pilocarpine effect on outflow facility following surgical disinsertion and retrodisplacement of the ciliary muscle from the scleral spur in the cynomolgus monkey. Invest Ophthalmol. 1976;15:793–807.PubMed
79.
Nakajima E, Nakajima T, Minagawa Y, Shearer TR, Azuma M. Contribution of ROCK in contraction of trabecular meshwork: proposed mechanism for regulating aqueous outflow in monkey and human eyes. J Pharma Sci. 2005;94:701–8.CrossRef
80.
Inoue T, Pecen P, Maddala R, Skiba NP, Pattabiraman PP, Epstein DL, et al. Characterization of cytoskeleton-enriched protein fraction of the trabecular meshwork and ciliary muscle cells. Invest Ophthalmol Vis Sci. 2010;51:6461–71.PubMedPubMedCentralCrossRef
81.
Xin C, Wang RK, Song S, Shen T, Wen J, Martin E, et al. Aqueous outflow regulation: Optical coherence tomography implicates pressure-dependent tissue motion. Exp Eye Res. 2017;158:171–86.PubMedCrossRef
82.
83.
Li G, Mukherjee D, Navarro I, Ashpole NE, Sherwood JM, Chang J, et al. Visualization of conventional outflow tissue responses to netarsudil in living mouse eyes. Eur J Pharmacol. 2016;787:20–31.PubMedPubMedCentralCrossRef
84.
Tanihara H, Inatani M, Honjo M, Tokushige H, Azuma J, Araie M. Intraocular pressure-lowering effects and safety of topical administration of a selective ROCK inhibitor, SNJ-1656, in healthy volunteers. Arch Ophthalmol. 2008;126:309–15.PubMedCrossRef
85.
Skaat A, Jasien JV, Ritch R. Efficacy of topically administered Rho-kinase inhibitor AR-12286 in patients with exfoliation syndrome and ocular hypertension or glaucoma. J Glaucoma. 2016;25:e807–14.PubMedCrossRef
86.
Williams RD, Novack GD, van Haarlem T, Kopczynski C. Ocular hypotensive effect of the Rho kinase inhibitor AR-12286 in patients with glaucoma and ocular hypertension. Am J Ophthalmol. 2011;152(834–41):e1.
87.
Lewis RA, Levy B, Ramirez N, Kopczynski CC, Usner DW, Novack GD. Correction: fixed-dose combination of AR-13324 and latanoprost: a double-masked, 28-day, randomised, controlled study in patients with open-angle glaucoma or ocular hypertension. Br J Ophthalmol. 2016;100:1016.CrossRef
88.
Bacharach J, Dubiner HB, Levy B, Kopczynski CC, Novack GD. Double-masked, randomized, dose-response study of AR-13324 versus latanoprost in patients with elevated intraocular pressure. Ophthalmology. 2015;122:302–7.PubMedCrossRef
89.
Lewis RA, Levy B, Ramirez N, Kopczynski CC, Usner DW, Novack GD. Fixed-dose combination of AR-13324 and latanoprost: a double-masked, 28-day, randomised, controlled study in patients with open-angle glaucoma or ocular hypertension. Br J Ophthalmol. 2016;100:339–44.PubMedCrossRef
90.
Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Araie M. Phase 2 randomized clinical study of a Rho kinase inhibitor, K-115, in primary open-angle glaucoma and ocular hypertension. Am J Ophthalmol. 2013;156:731–6.PubMedCrossRef
91.
Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Suganami H, et al. Additive intraocular pressure-lowering effects of the Rho kinase inhibitor ripasudil (K-115) combined with timolol or latanoprost: a report of 2 randomized clinical trials. JAMA Ophthalmol. 2015;133:755–61.PubMedCrossRef
92.
93.
Inazaki H, Kobayashi S, Anzai Y, Satoh H, Sato S, Inoue M, et al. Efficacy of the additional use of ripasudil, a Rho-kinase inhibitor, in patients with glaucoma inadequately controlled under maximum medical therapy. J Glaucoma. 2017;26:96–100.PubMed
94.
Inazaki H, Kobayashi S, Anzai Y, Satoh H, Sato S, Inoue M, et al. One-year efficacy of adjunctive use of Ripasudil, a Rho-kinase inhibitor, in patients with glaucoma inadequately controlled with maximum medical therapy. Graefes Arch Clin Exp Ophthalmol. 2017;255:2009–15.PubMedCrossRef
95.
Matsumura R, Inoue T, Matsumura A, Tanihara H. Efficacy of ripasudil as a second-line medication in addition to a prostaglandin analog in patients with exfoliation glaucoma: a pilot study. Clin Drug Invest. 2017;37:535–9.CrossRef
96.
Sato S, Hirooka K, Nitta E, Ukegawa K, Tsujikawa A. Additive intraocular pressure lowering effects of the Rho kinase inhibitor, ripasudil in glaucoma patients not able to obtain adequate control after other maximal tolerated medical therapy. Adv Ther. 2016;33:1628–34.PubMedCrossRef
97.
Terao E, Nakakura S, Fujisawa Y, Fujio Y, Matsuya K, Kobayashi Y, et al. Time course of conjunctival hyperemia induced by a Rho-kinase inhibitor anti-glaucoma eye drop: ripasudil 0.4. Curr Eye Res. 2017;42:738–42.PubMedCrossRef
98.
Nakagawa H, Koizumi N, Okumura N, Suganami H, Kinoshita S. Morphological changes of human corneal endothelial cells after Rho-associated kinase inhibitor eye drop (ripasudil) administration: a prospective open-label clinical study. PLoS One. 2015;10:e0136802.PubMedPubMedCentralCrossRef
99.
Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Fukushima A, et al. One-year clinical evaluation of 0.4% ripasudil (K-115) in patients with open-angle glaucoma and ocular hypertension. Acta Ophthalmol. 2016;94:e26–34.PubMedCrossRef
100.
Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Suganami H, et al. Intra-ocular pressure-lowering effects of a Rho kinase inhibitor, ripasudil (K-115), over 24 hours in primary open-angle glaucoma and ocular hypertension: a randomized, open-label, crossover study. Acta Ophthalmol. 2015;93:e254–60.PubMedCrossRef
101.
Tanna AP, Rademaker AW, Stewart WC, Feldman RM. Meta-analysis of the efficacy and safety of alpha2-adrenergic agonists, beta-adrenergic antagonists, and topical carbonic anhydrase inhibitors with prostaglandin analogs. Arch Ophthalmol. 2010;128:825–33.PubMedCrossRef
102.
Kitazawa Y, Araie M. Double-masked, phase III comparative study of the combination ophthalmic solution of the 1% dorzolamide hydrochloride/0.5% timolol maleate (MK-0507A) in patients with glaucoma and ocular hypertension. Nippon Ganka Gakkai Zasshi. 2011;115:495–507 (in Japanese).PubMed
103.
Harris A, Sergott RC, Spaeth GL, Katz JL, Shoemaker JA, Martin BJ. Color Doppler analysis of ocular vessel blood velocity in normal-tension glaucoma. Am J Ophthalmol. 1994;118:642–9.PubMedCrossRef
104.
Rankin SJ. Color Doppler imaging of the retrobulbar circulation in glaucoma. Surv Ophthalmol. 1999;43(Suppl 1):S176–82.PubMedCrossRef
105.
Nakabayashi S, Kawai M, Yoshioka T, Song YS, Tani T, Yoshida A, et al. Effect of intravitreal Rho kinase inhibitor ripasudil (K-115) on feline retinal microcirculation. Exp Eye Res. 2015;139:132–5.PubMedCrossRef
106.
Sugiyama T, Shibata M, Kajiura S, Okuno T, Tonari M, Oku H, et al. Effects of fasudil, a Rho-associated protein kinase inhibitor, on optic nerve head blood flow in rabbits. Invest Ophthalmol Vis Sci. 2011;52:64–9.PubMedCrossRef
107.
Watabe H, Abe S, Yoshitomi T. Effects of Rho-associated protein kinase inhibitors Y-27632 and Y-39983 on isolated rabbit ciliary arteries. Jpn J Ophthalmol. 2011;55:411–7.PubMedCrossRef
108.
Ohta Y, Takaseki S, Yoshitomi T. Effects of ripasudil hydrochloride hydrate (K-115), a Rho-kinase inhibitor, on ocular blood flow and ciliary artery smooth muscle contraction in rabbits. Jpn J Ophthalmol. 2017;5:423–32.CrossRef
109.
Flammer J, Orgul S, Costa VP, Orzalesi N, Krieglstein GK, Serra LM, et al. The impact of ocular blood flow in glaucoma. Prog Retin Eye Res. 2002;21:359–93.PubMedCrossRef
110.
Goldhagen B, Proia AD, Epstein DL, Rao PV. Elevated levels of RhoA in the optic nerve head of human eyes with glaucoma. J Glaucoma. 2012;21:530–8.PubMedCrossRef
111.
Tura A, Schuettauf F, Monnier PP, Bartz-Schmidt KU, Henke-Fahle S. Efficacy of Rho-kinase inhibition in promoting cell survival and reducing reactive gliosis in the rodent retina. Invest Ophthalmol Vis Sci. 2009;50:452–61.PubMedCrossRef
112.
Hirata A, Inatani M, Inomata Y, Yonemura N, Kawaji T, Honjo M, et al. Y-27632, a Rho-associated protein kinase inhibitor, attenuates neuronal cell death after transient retinal ischemia. Graefes Arch Clin Exp Ophthalmol. 2008;246:51–9.PubMedCrossRef
113.
Kitaoka Y, Kitaoka Y, Kumai T, Lam TT, Kuribayashi K, Isenoumi K, et al. Involvement of RhoA and possible neuroprotective effect of fasudil, a Rho kinase inhibitor, in NMDA-induced neurotoxicity in the rat retina. Brain Res. 2004;1018:111–8.PubMedCrossRef
114.
Bermel C, Tönges L, Planchamp V, Gillardon F, Weishaupt JH, Dietz GPH, et al. Combined inhibition of Cdk5 and ROCK additively increase cell survival, but not the regenerative response in regenerating retinal ganglion cells. Mol and Cell Neurosci. 2009;42:427–37.CrossRef
115.
Sagawa H, Terasaki H, Nakamura M, Ichikawa M, Yata T, Tokita Y, et al. A novel ROCK inhibitor, Y-39983, promotes regeneration of crushed axons of retinal ganglion cells into the optic nerve of adult cats. Exp Neurol. 2007;205:230–40.PubMedCrossRef
116.
Van de Velde S, De Groef L, Stalmans I, Moons L, Van Hove I. Toward axonal regeneration and neuroprotection in glaucoma: Rho kinase inhibitors as promising therapeutics. Prog Neurobiol. 2015;131:105–19.PubMedCrossRef
117.
Yamamoto K, Maruyama K, Himori N, Omodaka K, Yokoyama Y, Shiga Y, et al. The novel Rho kinase (ROCK) inhibitor K-115: a new candidate drug for neuroprotective treatment in glaucoma. Invest Ophthalmol Vis Sci. 2014;55:7126–36.PubMedCrossRef
118.
Kitaoka Y, Sase K, Tsukahara C, Kojima K, Shiono A, Kogo J, et al. Axonal Protection by ripasudil, a Rho kinase inhibitor, via modulating autophagy in TNF-induced optic nerve degeneration. Invest Ophthalmol Vis Sci. 2017;58:5056–64.PubMedCrossRef
119.
Occleston NL, Daniels JT, Tarnuzzer RW, Sethi KK, Alexander RA, Bhattacharya SS, et al. Single exposures to antiproliferatives: long-term effects on ocular fibroblast wound-healing behavior. Invest Ophthalmol Vis Sci. 1997;38:1998–2007.PubMed
120.
Khaw PT, Occleston NL, Schultz G, Grierson I, Sherwood MB, Larkin G. Activation and suppression of fibroblast function. Eye. 1994;8:188–95.PubMedCrossRef
121.
Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol. 2002;3:349–63.PubMedCrossRef
122.
Hinz B, Mastrangelo D, Iselin CE, Chaponnier C, Gabbiani G. Mechanical tension controls granulation tissue contractile activity and myofibroblast differentiation. Am J Pathol. 2001;159:1009–20.PubMedPubMedCentralCrossRef
123.
Meyer-ter-Vehn T, Sieprath S, Katzenberger B, Gebhardt S, Grehn F, Schlunck G. Contractility as a prerequisite for TGF-beta-induced myofibroblast transdifferentiation in human tenon fibroblasts. Invest Ophthalmol Vis Sci. 2006;47:4895–904.PubMedCrossRef
124.
Van de Velde S, Van Bergen T, Vandewalle E, Kindt N, Castermans K, Moons L, et al. Rho kinase inhibitor AMA0526 improves surgical outcome in a rabbit model of glaucoma filtration surgery. Prog Brain Res. 2015;220:283–97.PubMedCrossRef
125.
Futakuchi A, Inoue T, Fujimoto T, Inoue-Mochita M, Kawai M, Tanihara H. The effects of ripasudil (K-115), a Rho kinase inhibitor, on activation of human conjunctival fibroblasts. Exp Eye Res. 2016;149:107–15.PubMedCrossRef
126.
Kojima S, Sugiyama T, Takai S, Jin D, Ueki M, Oku H, et al. Effects of ripasudil, a Rho-associated protein kinase inhibitor, on conjunctival scarring in a canine filtration surgery model. Curr Top Pharmacol. 2015;19:67–73.
127.
SundarRaj N, Kinchington PR, Wessel H, Goldblatt B, Hassell J, Vergnes JP, et al. A Rho-associated protein kinase: differentially distributed in limbal and corneal epithelia. Invest Ophthalmol Vis Sci. 1998;39:1266–72.PubMed
128.
129.
Anderson SC, Stone C, Tkach L, SundarRaj N. Rho and Rho-kinase (ROCK) signaling in adherens and gap junction assembly in corneal epithelium. Invest Ophthalmol Vis Sci. 2002;43:978–86.PubMed
130.
Kim A, Petroll WM. Microtubule regulation of corneal fibroblast morphology and mechanical activity in 3-D culture. Exp Eye Res. 2007;85:546–56.PubMedPubMedCentralCrossRef
131.
Kim A, Lakshman N, Petroll WM. Quantitative assessment of local collagen matrix remodeling in 3-D culture: the role of Rho kinase. Exp Cell Res. 2006;312:3683–92.PubMedPubMedCentralCrossRef
132.
Yin J, Yu FS. Rho kinases regulate corneal epithelial wound healing. Am J Physiol Cell Physiol. 2008;295:378–87.CrossRef
133.
Okumura N, Koizumi N, Ueno M, Sakamoto Y, Takahashi H, Hirata K, et al. Enhancement of corneal endothelium wound healing by Rho-associated kinase (ROCK) inhibitor eye drops. Br J Ophthalmol. 2011;95:1006–9.PubMedCrossRef
134.
Okumura N, Koizumi N, Kay EP, Ueno M, Sakamoto Y, Nakamura S, et al. The ROCK inhibitor eye drop accelerates corneal endothelium wound healing. Invest Ophthalmol Vis Sci. 2013;54:2493–502.PubMedCrossRef
135.
Pipparelli A, Arsenijevic Y, Thuret G, Gain P, Nicolas M, Majo F. ROCK inhibitor enhances adhesion and wound healing of human corneal endothelial cells. PLoS One. 2013;8:e62095.PubMedPubMedCentralCrossRef
136.
Okumura N, Inoue R, Okazaki Y, Nakano S, Nakagawa H, Kinoshita S, et al. Effect of the Rho Kinase Inhibitor Y-27632 on Corneal Endothelial Wound Healing. Invest Ophthalmol Vis Sci. 2015;56:6067–74.PubMedCrossRef
137.
138.
139.
Okumura N, Kakutani K, Inoue R, Matsumoto D, Shimada T, Nakahara M, et al. Generation and feasibility assessment of a new vehicle for cell-based therapy for treating corneal endothelial dysfunction. PLoS One. 2016;11:e0158427.PubMedPubMedCentralCrossRef
140.
141.
142.
Itoh K, Yoshioka K, Akedo H, Uehata M, Ishizaki T, Narumiya S. An essential part for Rho-associated kinase in the transcellular invasion of tumor cells. Nat Med. 1999;5:221–5.PubMedCrossRef
143.
Yoshizaki H, Ohba Y, Parrini MC, Dulyaninova NG, Bresnick AR, Mochizuki N, et al. Cell type-specific regulation of RhoA activity during cytokinesis. J Biol Chem. 2004;279:44756–62.PubMedCrossRef
144.
Harvey SA, Anderson SC, SundarRaj N. Downstream effects of ROCK signaling in cultured human corneal stromal cells: microarray analysis of gene expression. Invest Ophthalmol Vis Sci. 2004;45:2168–76.PubMedCrossRef
145.
Yamada H, Yoneda M, Inaguma S, Gosho M, Murasawa Y, Isogai Z, et al. A Rho-associated kinase inhibitor protects permeability in a cell culture model of ocular disease, and reduces aqueous flare in anterior uveitis. J Ocul Pharmacol Ther. 2017;33:176–85.PubMedCrossRef
146.
Uchida T, Honjo M, Yamagishi R, Aihara M. The anti-inflammatory effect of ripasudil (K-115), a rho kinase (ROCK) inhibitor, on endotoxin-induced uveitis in rats. Invest Ophthalmol Vis Sci. 2017;58:5584–93.PubMedCrossRef
147.
Hollanders K, Hove IV, Sergeys J, Bergen TV, Lefevere E, Kindt N, et al. AMA0428, a potent rock inhibitor, attenuates early and late experimental diabetic retinopathy. Curr Eye Res. 2017;42:260–72.PubMedCrossRef
148.
Sijnave D, Van Bergen T, Castermans K, Kindt N, Vandewalle E, Stassen JM, et al. Inhibition of Rho-associated kinase prevents pathological wound healing and neovascularization after corneal trauma. Cornea. 2015;34:1120–9.PubMedCrossRef
Metadaten
Titel
Impact of the clinical use of ROCK inhibitor on the pathogenesis and treatment of glaucoma
verfasst von
Megumi Honjo
Hidenobu Tanihara
Publikationsdatum
14.02.2018
Verlag
Springer Japan
Erschienen in
Japanese Journal of Ophthalmology / Ausgabe 2/2018
Print ISSN: 0021-5155
Elektronische ISSN: 1613-2246
DOI
https://doi.org/10.1007/s10384-018-0566-9

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