Generic placeholder image

Current Drug Targets

Author(s): Junhui Wu, Jing Wei, Haoliang Chen, Yalong Dang* and Fang Lei*

DOI: 10.2174/0113894501286195231220094646

DownloadDownload PDF Flyer Cite As
Rho Kinase (ROCK) Inhibitors for the Treatment of Glaucoma

Page: [94 - 107] Pages: 14

  • * (Excluding Mailing and Handling)

Abstract

Glaucoma is the most common cause of irreversible blindness worldwide. It is characterized by progressive optic nerve degeneration and loss of visual field. Pathological increased intraocular pressure is its main modifiable risk factor. Rho kinase inhibitors are developed as a new class of glaucoma medication that increases outflow facility from the conventional aqueous humor outflow pathway. Additionally, they also have neuroprotective and anti-scarring effects that can might increase the success rate of glaucoma filtration surgery. This review aims to summarize the current concept of Rho kinase inhibitors in the treatment of glaucoma from beach to bedside.

[1]
Xu T, Wang B, Liu H, et al. Prevalence and causes of vision loss in China from 1990 to 2019: Findings from the global burden of disease study 2019. Lancet Public Health 2020; 5(12): e682-91.
[http://dx.doi.org/10.1016/S2468-2667(20)30254-1] [PMID: 33271081]
[2]
Jonas JB, Aung T, Bourne RR, Bron AM, Ritch R, Panda-Jonas S. Glaucoma. Lancet 2017; 390(10108): 2183-93.
[http://dx.doi.org/10.1016/S0140-6736(17)31469-1] [PMID: 28577860]
[3]
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(11): 2081-90.
[http://dx.doi.org/10.1016/j.ophtha.2014.05.013] [PMID: 24974815]
[4]
Neustaeter A, Vehof J, Snieder H, Jansonius NM. Glaucoma in large-scale population-based epidemiology: A questionnaire-based proxy. Eye (Lond) 2021; 35(2): 508-16.
[http://dx.doi.org/10.1038/s41433-020-0882-4] [PMID: 32555517]
[5]
Jayaram H, Kolko M, Friedman DS, Gazzard G. Glaucoma: Now and beyond. Lancet 2023; 402(10414): 1788-801.
[http://dx.doi.org/10.1016/S0140-6736(23)01289-8] [PMID: 37742700]
[6]
Leidl MC, Choi CJ, Syed ZA, Melki SA. Intraocular pressure fluctuation and glaucoma progression: What do we know? Br J Ophthalmol 2014; 98(10): 1315-9.
[http://dx.doi.org/10.1136/bjophthalmol-2013-303980] [PMID: 24627247]
[7]
Lee SSY, Mackey DA. Glaucoma – risk factors and current challenges in the diagnosis of a leading cause of visual impairment. Maturitas 2022; 163: 15-22.
[http://dx.doi.org/10.1016/j.maturitas.2022.05.002] [PMID: 35597227]
[8]
Aboobakar IF, Wiggs JL. The genetics of glaucoma: Disease associations, personalised risk assessment and therapeutic opportunities-A review. Clin Exp Ophthalmol 2022; 50(2): 143-62.
[http://dx.doi.org/10.1111/ceo.14035] [PMID: 35037362]
[9]
Hu X, Zhao GL, Xu MX, et al. Interplay between Müller cells and microglia aggravates retinal inflammatory response in experimental glaucoma. J Neuroinflammation 2021; 18(1): 303.
[http://dx.doi.org/10.1186/s12974-021-02366-x] [PMID: 34952606]
[10]
Liu M, Li H, Yang R, Ji D, Xia X. GSK872 and necrostatin-1 protect retinal ganglion cells against necroptosis through inhibition of RIP1/RIP3/MLKL pathway in glutamate-induced retinal excitotoxic model of glaucoma. J Neuroinflammation 2022; 19(1): 262.
[http://dx.doi.org/10.1186/s12974-022-02626-4] [PMID: 36289519]
[11]
Reina-Torres E, De Ieso ML, Pasquale LR, et al. The vital role for nitric oxide in intraocular pressure homeostasis. Prog Retin Eye Res 2021; 83: 100922.
[http://dx.doi.org/10.1016/j.preteyeres.2020.100922] [PMID: 33253900]
[12]
Quigley HA. Glaucoma. Lancet 2011; 377(9774): 1367-77.
[http://dx.doi.org/10.1016/S0140-6736(10)61423-7] [PMID: 21453963]
[13]
Chakrabarti A, Mohan N, Nazm N, Mehta R, Edward D. Newer advances in medical management of glaucoma. Indian J Ophthalmol 2022; 70(6): 1920-30.
[http://dx.doi.org/10.4103/ijo.IJO_2239_21] [PMID: 35647957]
[14]
Carreon T, van der Merwe E, Fellman RL, Johnstone M, Bhattacharya SK. Aqueous outflow - A continuum from trabecular meshwork to episcleral veins. Prog Retin Eye Res 2017; 57: 108-33.
[http://dx.doi.org/10.1016/j.preteyeres.2016.12.004] [PMID: 28028002]
[15]
Costagliola C, dell’Omo R, Agnifili L, et al. How many aqueous humor outflow pathways are there? Surv Ophthalmol 2020; 65(2): 144-70.
[http://dx.doi.org/10.1016/j.survophthal.2019.10.002] [PMID: 31622628]
[16]
Gabelt BAT, Kaufman PL. Changes in aqueous humor dynamics with age and glaucoma. Prog Retin Eye Res 2005; 24(5): 612-37.
[http://dx.doi.org/10.1016/j.preteyeres.2004.10.003] [PMID: 15919228]
[17]
Mallick S, Sharma M, Kumar A, Du Y. Cell-based therapies for trabecular meshwork regeneration to treat glaucoma. Biomolecules 2021; 11(9): 1258.
[http://dx.doi.org/10.3390/biom11091258] [PMID: 34572471]
[18]
Kerr NM. The changing glaucoma treatment paradigm. Clin Exp Ophthalmol 2022; 50(2): 126-7.
[http://dx.doi.org/10.1111/ceo.14052] [PMID: 35174602]
[19]
Grewe R. [The history of glaucoma]. Klin Monatsbl Augenheilkd 1986; 188(2): 167-9.
[http://dx.doi.org/10.1055/s-2008-1050606] [PMID: 3520122]
[20]
Hwang JS, Shin YJ. Role of choline in ocular diseases. Int J Mol Sci 2021; 22(9): 4733.
[http://dx.doi.org/10.3390/ijms22094733] [PMID: 33946979]
[21]
Erickson-Lamy KA, Nathanson JA. Epinephrine increases facility of outflow and cyclic AMP content in the human eye in vitro. Invest Ophthalmol Vis Sci 1992; 33(9): 2672-8.
[PMID: 1353486]
[22]
Tejwani S, Machiraju P, Nair AP, et al. Treatment of glaucoma by prostaglandin agonists and beta-blockers in combination directly reduces pro-fibrotic gene expression in trabecular meshwork. J Cell Mol Med 2020; 24(9): 5195-204.
[http://dx.doi.org/10.1111/jcmm.15172] [PMID: 32267082]
[23]
Wu X, Yang X, Liang Q, et al. Drugs for the treatment of glaucoma: Targets, structure-activity relationships and clinical research. Eur J Med Chem 2021; 226: 113842.
[http://dx.doi.org/10.1016/j.ejmech.2021.113842] [PMID: 34536672]
[24]
Brooks AMV, Gillies WE. Ocular beta-blockers in glaucoma management. Clinical pharmacological aspects. Drugs Aging 1992; 2(3): 208-21.
[http://dx.doi.org/10.2165/00002512-199202030-00005] [PMID: 1351412]
[25]
Skov AG, Rives AS, Freiberg J, Virgili G, Azuara-Blanco A, Kolko M. Comparative efficacy and safety of preserved versus preservative-free beta-blockers in patients with glaucoma or ocular hypertension: A systematic review. Acta Ophthalmol 2022; 100(3): 253-61.
[http://dx.doi.org/10.1111/aos.14926] [PMID: 34128326]
[26]
Stoner A, Harris A, Oddone F, et al. Topical carbonic anhydrase inhibitors and glaucoma in 2021: Where do we stand? Br J Ophthalmol 2022; 106(10): 1332-7.
[http://dx.doi.org/10.1136/bjophthalmol-2021-319530] [PMID: 34433550]
[27]
Toris CB, Camras CB, Yablonski ME, Brubaker RF. Effects of exogenous prostaglandins on aqueous humor dynamics and blood-aqueous barrier function. Surv Ophthalmol 1997; 41 (Suppl. 2): S69-75.
[http://dx.doi.org/10.1016/S0039-6257(97)80010-0] [PMID: 9154279]
[28]
Perry CM, McGavin JK, Culy CR, Ibbotson T. Latanoprost. Drugs Aging 2003; 20(8): 597-630.
[http://dx.doi.org/10.2165/00002512-200320080-00005] [PMID: 12795627]
[29]
Subbulakshmi S, Kavitha S, Venkatesh R. Prostaglandin analogs in ophthalmology. Indian J Ophthalmol 2023; 71(5): 1768-76.
[http://dx.doi.org/10.4103/IJO.IJO_2706_22] [PMID: 37203029]
[30]
Isobe T, Mizuno K, Kaneko Y, Ohta M, Koide T, Tanabe S. Effects of K-115, a rho-kinase inhibitor, on aqueous humor dynamics in rabbits. Curr Eye Res 2014; 39(8): 813-22.
[http://dx.doi.org/10.3109/02713683.2013.874444] [PMID: 24502505]
[31]
Wang J, Liu X, Zhong Y. Rho/Rho-associated kinase pathway in glaucoma. Int J Oncol 2013; 43(5): 1357-67.
[http://dx.doi.org/10.3892/ijo.2013.2100] [PMID: 24042317]
[32]
Inoue T, Tanihara H. Rho-associated kinase inhibitors: A novel glaucoma therapy. Prog Retin Eye Res 2013; 37: 1-12.
[http://dx.doi.org/10.1016/j.preteyeres.2013.05.002] [PMID: 23770081]
[33]
Erschbamer MK, Hofstetter CP, Olson L, Rho A, Rho B, Rho C. RhoA, RhoB, RhoC, Rac1, Cdc42, and Tc10 mRNA levels in spinal cord, sensory ganglia, and corticospinal tract neurons and long-lasting specific changes following spinal cord injury. J Comp Neurol 2005; 484(2): 224-33.
[http://dx.doi.org/10.1002/cne.20471] [PMID: 15736231]
[34]
Hartmann S, Ridley AJ, Lutz S. The function of Rho-associated kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease. Front Pharmacol 2015; 6: 276.
[http://dx.doi.org/10.3389/fphar.2015.00276] [PMID: 26635606]
[35]
Pronk MCA, van Bezu JSM, van Nieuw Amerongen GP, van Hinsbergh VWM, Hordijk PL. RhoA, RhoB and RhoC differentially regulate endothelial barrier function. Small GTPases 2019; 10(6): 466-84.
[http://dx.doi.org/10.1080/21541248.2017.1339767] [PMID: 28949796]
[36]
Eckenstaler R, Hauke M, Benndorf RA. A current overview of RhoA, RhoB, and RhoC functions in vascular biology and pathology. Biochem Pharmacol 2022; 206: 115321.
[http://dx.doi.org/10.1016/j.bcp.2022.115321] [PMID: 36306821]
[37]
Jaffe AB, Hall A. RHO GTPASES: Biochemistry and biology. Annu Rev Cell Dev Biol 2005; 21(1): 247-69.
[http://dx.doi.org/10.1146/annurev.cellbio.21.020604.150721] [PMID: 16212495]
[38]
Mosaddeghzadeh N, Ahmadian MR. The RHO family GTPases: Mechanisms of regulation and signaling. Cells 2021; 10(7): 1831.
[http://dx.doi.org/10.3390/cells10071831] [PMID: 34359999]
[39]
Riento K, Ridley AJ. ROCKs: Multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol 2003; 4(6): 446-56.
[http://dx.doi.org/10.1038/nrm1128] [PMID: 12778124]
[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(2): 189-93.
[http://dx.doi.org/10.1016/0014-5793(96)00811-3] [PMID: 8772201]
[41]
Narumiya S, Thumkeo D. Rho signaling research: History, current status and future directions. FEBS Lett 2018; 592(11): 1763-76.
[http://dx.doi.org/10.1002/1873-3468.13087] [PMID: 29749605]
[42]
Loirand G. Rho kinases in health and disease: From basic science to translational research. Pharmacol Rev 2015; 67(4): 1074-95.
[http://dx.doi.org/10.1124/pr.115.010595] [PMID: 26419448]
[43]
Narumiya S. The small GTPase Rho: cellular functions and signal transduction. J Biochem 1996; 120(2): 215-28.
[http://dx.doi.org/10.1093/oxfordjournals.jbchem.a021401] [PMID: 8889802]
[44]
Dikopf MS, Vajaranant TS, Edward DP. Topical treatment of glaucoma: Established and emerging pharmacology. Expert Opin Pharmacother 2017; 18(9): 885-98.
[http://dx.doi.org/10.1080/14656566.2017.1328498] [PMID: 28480761]
[45]
Berrino E, Supuran CT. Rho-kinase inhibitors in the management of glaucoma. Expert Opin Ther Pat 2019; 29(10): 817-27.
[http://dx.doi.org/10.1080/13543776.2019.1670812] [PMID: 31573364]
[46]
Schmidt SI, Blaabjerg M, Freude K, Meyer M. RhoA signaling in neurodegenerative diseases. Cells 2022; 11(9): 1520.
[http://dx.doi.org/10.3390/cells11091520] [PMID: 35563826]
[47]
Barcelo J, Samain R, Sanz-Moreno V. Preclinical to clinical utility of ROCK inhibitors in cancer. Trends Cancer 2023; 9(3): 250-63.
[http://dx.doi.org/10.1016/j.trecan.2022.12.001] [PMID: 36599733]
[48]
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 Pharm Sci 2005; 94(4): 701-8.
[http://dx.doi.org/10.1002/jps.20285] [PMID: 15682386]
[49]
Rao PV, Deng P-F, Kumar J, Epstein DL. Modulation of aqueous humor outflow facility by the Rho kinase-specific inhibitor Y-27632. Invest Ophthalmol Vis Sci 2001; 42(5): 1029-37.
[PMID: 11274082]
[50]
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(8): 530-8.
[http://dx.doi.org/10.1097/IJG.0b013e318241b83c] [PMID: 22495072]
[51]
Honjo M, Tanihara H, Inatani M, et al. Effects of rho-associated protein kinase inhibitor Y-27632 on intraocular pressure and outflow facility. Invest Ophthalmol Vis Sci 2001; 42(1): 137-44.
[PMID: 11133858]
[52]
Ashwinbalaji S, Haribalaganesh R, Krishnadas S, Muthukkaruppan V, Senthilkumari S. SB772077B (SB77) alleviated the aqueous outflow resistance mediated by cyclic mechanical stress in perfused human cadaveric eyes. Sci Rep 2020; 10(1): 10202.
[http://dx.doi.org/10.1038/s41598-020-67087-2] [PMID: 32576873]
[53]
Lin CW, Sherman B, Moore LA, et al. Discovery and preclinical development of netarsudil, a novel ocular hypotensive agent for the treatment of glaucoma. J Ocul Pharmacol Ther 2018; 34(1-2): 40-51.
[http://dx.doi.org/10.1089/jop.2017.0023] [PMID: 28609185]
[54]
Yamagishi-Kimura R, Honjo M, Komizo T, et al. Interaction between pilocarpine and ripasudil on intraocular pressure, pupil diameter, and the aqueous-outflow pathway. Invest Ophthalmol Vis Sci 2018; 59(5): 1844-54.
[http://dx.doi.org/10.1167/iovs.18-23900] [PMID: 29677344]
[55]
Ashwinbalaji S, Senthilkumari S, Gowripriya C, et al. SB772077B, A new rho kinase inhibitor enhances aqueous humour outflow facility in human eyes. Sci Rep 2018; 8(1): 15472.
[http://dx.doi.org/10.1038/s41598-018-33932-8] [PMID: 30341380]
[56]
Van de Velde S, Van Bergen T, Sijnave D, et al. AMA0076, a novel, locally acting Rho kinase inhibitor, potently lowers intraocular pressure in New Zealand white rabbits with minimal hyperemia. Invest Ophthalmol Vis Sci 2014; 55(2): 1006-16.
[http://dx.doi.org/10.1167/iovs.13-13157] [PMID: 24474276]
[57]
Guan G, Cannon RD, Coates DE, Mei L. Effect of the Rho-Kinase/ROCK signaling pathway on cytoskeleton components. Genes 2023; 14(2): 272.
[http://dx.doi.org/10.3390/genes14020272] [PMID: 36833199]
[58]
Tamura M, Iwamoto Y, Nakatsuka K, Yamanouchi U. Immunofluorescence studies of the cytoskeletal and contractile elements in cultured human trabecular cells. Jpn J Ophthalmol 1989; 33(1): 95-102.
[PMID: 2659860]
[59]
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(2): 296-300.
[http://dx.doi.org/10.1006/bbrc.2001.5751] [PMID: 11606042]
[60]
Kaibuchi K, Kuroda S, Amano M. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells. Annu Rev Biochem 1999; 68(1): 459-86.
[http://dx.doi.org/10.1146/annurev.biochem.68.1.459] [PMID: 10872457]
[61]
Rosenthal R, Choritz L, Schlott S, et al. Effects of ML-7 and Y-27632 on carbachol- and endothelin-1-induced contraction of bovine trabecular meshwork. Exp Eye Res 2005; 80(6): 837-45.
[http://dx.doi.org/10.1016/j.exer.2004.12.013] [PMID: 15939040]
[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(2): 197-206.
[http://dx.doi.org/10.1016/j.exer.2004.08.029] [PMID: 15670798]
[63]
Renieri G, Choritz L, Rosenthal R, Meissner S, Pfeiffer N, Thieme H. Effects of endothelin-1 on calcium-independent contraction of bovine trabecular meshwork. Graefes Arch Clin Exp Ophthalmol 2008; 246(8): 1107-15.
[http://dx.doi.org/10.1007/s00417-008-0817-4] [PMID: 18401592]
[64]
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(6): 470-4.
[http://dx.doi.org/10.1076/ceyr.22.6.470.5489] [PMID: 11584347]
[65]
Rohen JW, van der Zypen E. The phagocytic activity of the trabecularmeshwork endothelium. An electron-microscopic study of the vervet (Cercopithecus aethiops). Graefes Arch Clin Exp Ophthalmol 1968; 175(2): 143-60.
[http://dx.doi.org/10.1007/BF02385060] [PMID: 4175056]
[66]
Sherwood ME, Richardson TM. Phagocytosis by trabecular meshwork cells: Sequence of events in cats and monkeys. Exp Eye Res 1988; 46(6): 881-95.
[http://dx.doi.org/10.1016/S0014-4835(88)80040-X] [PMID: 3197758]
[67]
Buller C, Johnson DH, Tschumper RC. Human trabecular meshwork phagocytosis. Observations in an organ culture system. Invest Ophthalmol Vis Sci 1990; 31(10): 2156-63.
[PMID: 2211012]
[68]
Grierson I, Chisholm IA. Clearance of debris from the iris through the drainage angle of the rabbit’s eye. Br J Ophthalmol 1978; 62(10): 694-704.
[http://dx.doi.org/10.1136/bjo.62.10.694] [PMID: 708671]
[69]
Johnson DH, Richardson TM, Epstein DL. Trabecular meshwork recovery after phagocytic challenge. Curr Eye Res 1989; 8(11): 1121-30.
[http://dx.doi.org/10.3109/02713688909000037] [PMID: 2612200]
[70]
Wang C, Dang Y, Waxman S, et al. Ripasudil in a model of pigmentary glaucoma. Transl Vis Sci Technol 2020; 9(10): 27-7.
[http://dx.doi.org/10.1167/tvst.9.10.27] [PMID: 33024620]
[71]
Dang Y, Wang C, Shah P, Waxman S, Loewen RT, Loewen NA. RKI-1447, a Rho kinase inhibitor, causes ocular hypotension, actin stress fiber disruption, and increased phagocytosis. Graefes Arch Clin Exp Ophthalmol 2019; 257(1): 101-9.
[http://dx.doi.org/10.1007/s00417-018-4175-6] [PMID: 30456419]
[72]
Chen W, Yang X, Fang J, Zhang Y, Zhu W, Yang X. Rho-associated protein kinase inhibitor treatment promotes proliferation and phagocytosis in trabecular meshwork cells. Front Pharmacol 2020; 11: 302.
[http://dx.doi.org/10.3389/fphar.2020.00302] [PMID: 32256367]
[73]
Fukunaga T, Ikesugi K, Nishio M, et al. The effect of the Rho-associated protein kinase inhibitor, HA-1077, in the rabbit ocular hypertension model induced by water loading. Curr Eye Res 2009; 34(1): 42-7.
[http://dx.doi.org/10.1080/02713680802531353] [PMID: 19172469]
[74]
Honjo M, Inatani M, Kido N, et al. Effects of protein kinase inhibitor, HA1077, on intraocular pressure and outflow facility in rabbit eyes. Arch Ophthalmol 2001; 119(8): 1171-8.
[http://dx.doi.org/10.1001/archopht.119.8.1171] [PMID: 11483085]
[75]
Nishio M, Fukunaga T, Sugimoto M, 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(4): 282-6.
[http://dx.doi.org/10.1080/02713680902783763] [PMID: 19373576]
[76]
Li G, Mukherjee D, Navarro I, et al. Visualization of conventional outflow tissue responses to netarsudil in living mouse eyes. Eur J Pharmacol 2016; 787: 20-31.
[http://dx.doi.org/10.1016/j.ejphar.2016.04.002] [PMID: 27085895]
[77]
Li G, Lee C, Read AT, et al. Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis. eLife 2021; 10: e60831.
[http://dx.doi.org/10.7554/eLife.60831] [PMID: 33783352]
[78]
Tian B, Kaufman PL. Effects of the Rho kinase inhibitor Y-27632 and the phosphatase inhibitor calyculin A on outflow facility in monkeys. Exp Eye Res 2005; 80(2): 215-25.
[http://dx.doi.org/10.1016/j.exer.2004.09.002] [PMID: 15670800]
[79]
Tokushige H, Inatani M, Nemoto S, et al. Effects of topical administration of y-39983, a selective rho-associated protein kinase inhibitor, on ocular tissues in rabbits and monkeys. Invest Ophthalmol Vis Sci 2007; 48(7): 3216-22.
[http://dx.doi.org/10.1167/iovs.05-1617] [PMID: 17591891]
[80]
Lu Z, Overby DR, Scott PA, Freddo TF, Gong H. The mechanism of increasing outflow facility by rho-kinase inhibition with Y-27632 in bovine eyes. Exp Eye Res 2008; 86(2): 271-81.
[http://dx.doi.org/10.1016/j.exer.2007.10.018] [PMID: 18155193]
[81]
Lu Z, Zhang Y, Freddo TF, Gong H. Similar hydrodynamic and morphological changes in the aqueous humor outflow pathway after washout and Y27632 treatment in monkey eyes. Exp Eye Res 2011; 93(4): 397-404.
[http://dx.doi.org/10.1016/j.exer.2011.05.012] [PMID: 21669200]
[82]
Ren R, Li G, Le TD, Kopczynski C, Stamer WD, Gong H. Netarsudil increases outflow facility in human eyes through multiple mechanisms. Invest Ophthalmol Vis Sci 2016; 57(14): 6197-209.
[http://dx.doi.org/10.1167/iovs.16-20189] [PMID: 27842161]
[83]
Kaneko Y, Ohta M, Inoue T, et al. Effects of K-115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm’s canal endothelial cells. Sci Rep 2016; 6(1): 19640.
[http://dx.doi.org/10.1038/srep19640] [PMID: 26782355]
[84]
Kameda T, Inoue T, Inatani M, et al. The effect of Rho-associated protein kinase inhibitor on monkey Schlemm’s canal endothelial cells. Invest Ophthalmol Vis Sci 2012; 53(6): 3092-103.
[http://dx.doi.org/10.1167/iovs.11-8018] [PMID: 22491412]
[85]
Overby D, Gong H, Qiu G, Freddo TF, Johnson M. The mechanism of increasing outflow facility during washout in the bovine eye. Invest Ophthalmol Vis Sci 2002; 43(11): 3455-64.
[PMID: 12407156]
[86]
Torrejon KY, Papke EL, Halman JR, et al. TGFβ2-induced outflow alterations in a bioengineered trabecular meshwork are offset by a rho-associated kinase inhibitor. Sci Rep 2016; 6(1): 38319.
[http://dx.doi.org/10.1038/srep38319] [PMID: 27924833]
[87]
Ota C, Ida Y, Ohguro H, Hikage F. ROCK inhibitors beneficially alter the spatial configuration of TGFβ2-treated 3D organoids from a human trabecular meshwork (HTM). Sci Rep 2020; 10(1): 20292.
[http://dx.doi.org/10.1038/s41598-020-77302-9] [PMID: 33219246]
[88]
Buffault J, Brignole-Baudouin F, Reboussin É, et al. The dual effect of Rho-kinase inhibition on trabecular meshwork cells cytoskeleton and extracellular matrix in an in vitro model of glaucoma. J Clin Med 2022; 11(4): 1001.
[http://dx.doi.org/10.3390/jcm11041001] [PMID: 35207274]
[89]
Tanna AP, Johnson M. Rho Kinase inhibitors as a novel treatment for glaucoma and ocular hypertension. Ophthalmology 2018; 125(11): 1741-56.
[http://dx.doi.org/10.1016/j.ophtha.2018.04.040] [PMID: 30007591]
[90]
Rao VP, Epstein DL. Rho GTPase/Rho kinase inhibition as a novel target for the treatment of glaucoma. BioDrugs 2007; 21(3): 167-77.
[http://dx.doi.org/10.2165/00063030-200721030-00004] [PMID: 17516712]
[91]
Challa P, Arnold JJ. Rho-kinase inhibitors offer a new approach in the treatment of glaucoma. Expert Opin Investig Drugs 2014; 23(1): 81-95.
[http://dx.doi.org/10.1517/13543784.2013.840288] [PMID: 24094075]
[92]
Schehlein EM, Robin AL. Rho-associated kinase inhibitors: Evolving strategies in glaucoma treatment. Drugs 2019; 79(10): 1031-6.
[http://dx.doi.org/10.1007/s40265-019-01130-z] [PMID: 31134520]
[93]
Garnock-Jones KP. Ripasudil: First global approval. Drugs 2014; 74(18): 2211-5.
[http://dx.doi.org/10.1007/s40265-014-0333-2] [PMID: 25414122]
[94]
Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Araie M. Phase 1 clinical trials of a selective Rho kinase inhibitor, K-115. JAMA Ophthalmol 2013; 131(10): 1288-95.
[http://dx.doi.org/10.1001/jamaophthalmol.2013.323] [PMID: 23787820]
[95]
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(4): 731-736.e2.
[http://dx.doi.org/10.1016/j.ajo.2013.05.016] [PMID: 23831221]
[96]
Tanihara H, Inoue T, Yamamoto T, 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(4): e254-60.
[http://dx.doi.org/10.1111/aos.12599] [PMID: 25487877]
[97]
Tanihara H, Inoue T, Yamamoto T, 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(7): 755-61.
[http://dx.doi.org/10.1001/jamaophthalmol.2015.0525] [PMID: 25880207]
[98]
Tanihara H, Inoue T, Yamamoto T, 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(1): e26-34.
[http://dx.doi.org/10.1111/aos.12829] [PMID: 26338317]
[99]
Tanihara H, Kakuda T, Sano T, et al. Safety and efficacy of ripasudil in Japanese patients with glaucoma or ocular hypertension: 3-month interim analysis of ROCK-J, a post-marketing surveillance study. Adv Ther 2019; 36(2): 333-43.
[http://dx.doi.org/10.1007/s12325-018-0863-1] [PMID: 30610614]
[100]
Tanihara H, Kakuda T, Sano T, Kanno T, Gunji R. Safety and efficacy of ripasudil in Japanese patients with glaucoma or ocular hypertension: 12-month interim analysis of ROCK-J, a post-marketing surveillance study. BMC Ophthalmol 2020; 20(1): 275.
[http://dx.doi.org/10.1186/s12886-020-01490-1] [PMID: 32646383]
[101]
Tanihara H, Kakuda T, Sano T, Kanno T, Kurihara Y. Long-term intraocular pressure-lowering effects and adverse events of ripasudil in patients with glaucoma or ocular hypertension over 24 months. Adv Ther 2022; 39(4): 1659-77.
[http://dx.doi.org/10.1007/s12325-021-02023-y] [PMID: 35150417]
[102]
Havens S J, Gulati V. Neovascular glaucoma. Retinal pharmacotherapeutics 2016; 55: 196-204.
[103]
Futakuchi A, Morimoto T, Ikeda Y, et al. Intraocular pressure-lowering effects of ripasudil in uveitic glaucoma, exfoliation glaucoma, and steroid-induced glaucoma patients: ROCK-S, a multicentre historical cohort study. Sci Rep 2020; 10(1): 10308.
[http://dx.doi.org/10.1038/s41598-020-66928-4] [PMID: 32587304]
[104]
Saito H, Kagami S, Mishima K, Mataki N, Fukushima A, Araie M. Long-term side effects including blepharitis leading to discontinuation of ripasudil. J Glaucoma 2019; 28(4): 289-93.
[http://dx.doi.org/10.1097/IJG.0000000000001203] [PMID: 30720574]
[105]
Hoy SM. Netarsudil ophthalmic solution 0.02%: First global approval. Drugs 2018; 78(3): 389-96.
[http://dx.doi.org/10.1007/s40265-018-0877-7] [PMID: 29453668]
[106]
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(1): 51-4.
[http://dx.doi.org/10.1097/IJG.0b013e3182952213] [PMID: 25535688]
[107]
Kiel JW, Kopczynski CC. Effect of AR-13324 on episcleral venous pressure in Dutch belted rabbits. J Ocul Pharmacol Ther 2015; 31(3): 146-51.
[http://dx.doi.org/10.1089/jop.2014.0146] [PMID: 25756366]
[108]
Sit AJ, Gupta D, Kazemi A, et al. Netarsudil improves trabecular outflow facility in patients with primary open angle glaucoma or ocular hypertension: A phase 2 study. Am J Ophthalmol 2021; 226: 262-9.
[http://dx.doi.org/10.1016/j.ajo.2021.01.019] [PMID: 33524367]
[109]
Levy B, Ramirez N, Novack GD, Kopczynski C. Ocular hypotensive safety and systemic absorption of AR-13324 ophthalmic solution in normal volunteers. Am J Ophthalmol 2015; 159(5): 980-985.e1.
[http://dx.doi.org/10.1016/j.ajo.2015.01.026] [PMID: 25637177]
[110]
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(2): 302-7.
[http://dx.doi.org/10.1016/j.ophtha.2014.08.022] [PMID: 25270273]
[111]
Serle JB, Katz LJ, McLaurin E, et al. Two phase 3 clinical trials comparing the safety and efficacy of netarsudil to timolol in patients with elevated intraocular pressure: Rho kinase elevated IOP treatment trial 1 and 2 (ROCKET-1 and ROCKET-2). Am J Ophthalmol 2018; 186: 116-27.
[http://dx.doi.org/10.1016/j.ajo.2017.11.019] [PMID: 29199013]
[112]
Khouri AS, Serle JB, Bacharach J, et al. Once-daily netarsudil versus twice-daily timolol in patients with elevated intraocular pressure: The randomized phase 3 ROCKET-4 study. Am J Ophthalmol 2019; 204: 97-104.
[http://dx.doi.org/10.1016/j.ajo.2019.03.002] [PMID: 30862500]
[113]
Oydanich M, Roll E H, Uppuluri S, Khouri A S. Effectiveness of netarsudil 0.02% in lowering intraocular pressure in patients with secondary glaucoma. Canad J Ophthalmol 2023.
[114]
Lewis RA, Levy B, Ramirez N, C Kopczynski C, 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(3): 339-44.
[http://dx.doi.org/10.1136/bjophthalmol-2015-306778] [PMID: 26209587]
[115]
Asrani S, Robin AL, Serle JB, et al. Netarsudil/latanoprost fixed-dose combination for elevated intraocular pressure: three-month data from a randomized phase 3 trial. Am J Ophthalmol 2019; 207: 248-57.
[http://dx.doi.org/10.1016/j.ajo.2019.06.016] [PMID: 31229466]
[116]
Brubaker JW, Teymoorian S, Lewis RA, et al. One year of netarsudil and latanoprost fixed-dose combination for elevated intraocular pressure: Phase 3, randomized MERCURY-1 study. Ophthalmol Glaucoma 2020; 3(5): 327-38.
[http://dx.doi.org/10.1016/j.ogla.2020.05.008] [PMID: 32768361]
[117]
Walters TR, Ahmed IIK, Lewis RA, et al. Once-daily netarsudil/latanoprost fixed-dose combination for elevated intraocular pressure in the randomized phase 3 MERCURY-2 study. Ophthalmol Glaucoma 2019; 2(5): 280-9.
[http://dx.doi.org/10.1016/j.ogla.2019.03.007] [PMID: 32672669]
[118]
Wang T, Zhang Y, Chi M, et al. A novel fixed-combination timolol-netarsudil-latanoprost ophthalmic solution for the treatment of glaucoma and ocular hypertension. Asian J Pharm Sci 2022; 17(6): 938-48.
[http://dx.doi.org/10.1016/j.ajps.2022.11.001] [PMID: 36600899]
[119]
Kopczynski C, Novack GD, Swearingen D, van Haarlem T. Ocular hypotensive efficacy, safety and systemic absorption of AR-12286 ophthalmic solution in normal volunteers. Br J Ophthalmol 2013; 97(5): 567-72.
[http://dx.doi.org/10.1136/bjophthalmol-2012-302466] [PMID: 23435190]
[120]
Ren R, Humphrey AA, Kopczynski C, Gong H. Rho kinase inhibitor AR-12286 reverses steroid-induced changes in intraocular pressure, effective filtration areas, and morphology in mouse eyes. Invest Ophthalmol Vis Sci 2023; 64(2): 7.
[http://dx.doi.org/10.1167/iovs.64.2.7] [PMID: 36734964]
[121]
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(5): 834-841.e1.
[http://dx.doi.org/10.1016/j.ajo.2011.04.012] [PMID: 21794845]
[122]
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(9): e807-14.
[http://dx.doi.org/10.1097/IJG.0000000000000508] [PMID: 27552517]
[123]
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(3): 309-15.
[http://dx.doi.org/10.1001/archophthalmol.2007.76] [PMID: 18332309]
[124]
Inoue T, Tanihara H, Tokushige H, Araie M. Efficacy and safety of SNJ -1656 in primary open-angle glaucoma or ocular hypertension. Acta Ophthalmol 2015; 93(5): e393-5.
[http://dx.doi.org/10.1111/aos.12641] [PMID: 25783615]
[125]
Shibuya M, Suzuki Y. [Treatment of cerebral vasospasm by a protein kinase inhibitor AT 877]. No To Shinkei 1993; 45(9): 819-24.
[PMID: 8217408]
[126]
Pakravan M, Beni AN, Ghahari E, 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(6): e676-80.
[http://dx.doi.org/10.1097/MJT.0000000000000362] [PMID: 26825486]
[127]
Van de Velde S, De Groef L, Stalmans I, Moons L, Van Hove I. Towards axonal regeneration and neuroprotection in glaucoma: Rho kinase inhibitors as promising therapeutics. Prog Neurobiol 2015; 131: 105-19.
[http://dx.doi.org/10.1016/j.pneurobio.2015.06.002] [PMID: 26093354]
[128]
Mueller BK, Mack H, Teusch N. Rho kinase, a promising drug target for neurological disorders. Nat Rev Drug Discov 2005; 4(5): 387-98.
[http://dx.doi.org/10.1038/nrd1719] [PMID: 15864268]
[129]
Yu J, Lin L, Luan X, Jing X, Maierab . Impacts of Rho kinase inhibitor Fasudil on Rho/ROCK signaling pathway in rabbits with optic nerve injury. Int J Clin Exp Pathol 2015; 8(11): 14717-24.
[PMID: 26823796]
[130]
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(10): 964-70.
[http://dx.doi.org/10.3109/02713683.2011.599106] [PMID: 21950703]
[131]
Sugiyama T, Shibata M, Kajiura S, 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(1): 64-9.
[http://dx.doi.org/10.1167/iovs.10-5265] [PMID: 20720232]
[132]
Sagawa H, Terasaki H, Nakamura M, 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(1): 230-40.
[http://dx.doi.org/10.1016/j.expneurol.2007.02.002] [PMID: 17359977]
[133]
Yang Z, Wang J, Liu X, Cheng Y, Deng L, Zhong Y. Y-39983 downregulates RhoA/Rho-associated kinase expression during its promotion of axonal regeneration. Oncol Rep 2013; 29(3): 1140-6.
[http://dx.doi.org/10.3892/or.2012.2205] [PMID: 23258382]
[134]
Lingor P, Teusch N, Schwarz K, et al. Inhibition of Rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo. J Neurochem 2007; 103(1): 181-9.
[http://dx.doi.org/10.1111/j.1471-4159.2007.04756.x] [PMID: 17608642]
[135]
Ichikawa M, Yoshida J, Saito K, Sagawa H, Tokita Y, Watanabe M. Differential effects of two ROCK inhibitors, Fasudil and Y-27632, on optic nerve regeneration in adult cats. Brain Res 2008; 1201: 23-33.
[http://dx.doi.org/10.1016/j.brainres.2008.01.063] [PMID: 18313036]
[136]
Shaw PX, Sang A, Wang Y, et al. Topical administration of a Rock/Net inhibitor promotes retinal ganglion cell survival and axon regeneration after optic nerve injury. Exp Eye Res 2017; 158: 33-42.
[http://dx.doi.org/10.1016/j.exer.2016.07.006] [PMID: 27443501]
[137]
Yamamoto K, Maruyama K, Himori N, 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(11): 7126-36.
[http://dx.doi.org/10.1167/iovs.13-13842] [PMID: 25277230]
[138]
Lim R. The surgical management of glaucoma: A review. Clin Exp Ophthalmol 2022; 50(2): 213-31.
[http://dx.doi.org/10.1111/ceo.14028] [PMID: 35037376]
[139]
Van de Velde S, Van Bergen T, Vandewalle E, et al. Rho kinase inhibitor AMA0526 improves surgical outcome in a rabbit model of glaucoma filtration surgery. Prog Brain Res 2015; 220: 283-97.
[http://dx.doi.org/10.1016/bs.pbr.2015.04.014] [PMID: 26497796]
[140]
Cabourne E, Clarke JCK, Schlottmann PG, Evans JR. Mitomycin C versus 5-Fluorouracil for wound healing in glaucoma surgery. Cochrane Libr 2015; 2015(11): CD006259.
[http://dx.doi.org/10.1002/14651858.CD006259.pub2] [PMID: 26545176]
[141]
Lama PJ, Fechtner RD. Antifibrotics and wound healing in glaucoma surgery. Surv Ophthalmol 2003; 48(3): 314-46.
[http://dx.doi.org/10.1016/S0039-6257(03)00038-9] [PMID: 12745005]
[142]
Cheng F, Shen Y, Mohanasundaram P, et al. Vimentin coordinates fibroblast proliferation and keratinocyte differentiation in wound healing via TGF-β–Slug signaling. Proc Natl Acad Sci USA 2016; 113(30): E4320-7.
[http://dx.doi.org/10.1073/pnas.1519197113] [PMID: 27466403]
[143]
Meyer-ter-Vehn T, Sieprath S, Katzenberger B, Gebhardt S, Grehn F, Schlunck G. Contractility as a prerequisite for TGF-β-induced myofibroblast transdifferentiation in human tenon fibroblasts. Invest Ophthalmol Vis Sci 2006; 47(11): 4895-904.
[http://dx.doi.org/10.1167/iovs.06-0118] [PMID: 17065504]
[144]
Ibrahim DG, Ko JA, Iwata W, Okumichi H, Kiuchi Y. An in vitro study of scarring formation mediated by human Tenon fibroblasts: Effect of Y-27632, a Rho kinase inhibitor. Cell Biochem Funct 2019; 37(2): 113-24.
[http://dx.doi.org/10.1002/cbf.3382] [PMID: 30773659]
[145]
Tura A, Grisanti S, Petermeier K, Henke-Fahle S. The Rho-kinase inhibitor H-1152P suppresses the wound-healing activities of human Tenon’s capsule fibroblasts in vitro. Invest Ophthalmol Vis Sci 2007; 48(5): 2152-61.
[http://dx.doi.org/10.1167/iovs.06-1271] [PMID: 17460274]
[146]
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(12): 5549-57.
[http://dx.doi.org/10.1167/iovs.07-0878] [PMID: 18055804]