| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 From the Departments of Ophthalmology and Visual Sciences and 2 Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, Japan; the 3 Department of Ophthalmology, Tenri Hospital, Tenri, Japan; the 4 Department of Bioscience, National Cardiovascular Center Research Institute, Osaka, Japan; the 5 Department of Molecular Pathophysiology, Graduate School of Pharmaceutical Sciences, Osaka, Japan; and the 6 Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine.
PURPOSE. To elucidate the roles of Rho-associated protein kinase (ROCK) in regulating intraocular pressure (IOP) and outflow facility in the rabbit eye.
METHODS. A specific ROCK inhibitor Y-27632 was used. The IOP, the outflow facility, and the pupil diameter were determined before and after the topical, intracameral, or intravitreal administration of Y-27632 in rabbits. Western blot analysis was used to identify specific ROCK isoform in human trabecular meshwork (TM) cells and bovine ciliary muscle (CM) tissues. The cell morphology and distribution of actin filaments and vinculin in TM cells were studied by cell biology techniques. Carbachol (Cch)-induced contraction of isolated bovine CM strips after administration of Y-27632 was measured in a perfusion chamber.
RESULTS. In rabbit eyes, administration of Y-27632 resulted in a significant decrease in IOP in a dose-dependent manner. An increase of the outflow facility and pupil size dilation was also observed in Y-27632–treated eyes. Western blot analysis revealed the presence of p160ROCK in human TM cells and bovine CM tissues. In cultured human TM cells, exposure to Y-27632 caused retraction and rounding of cell bodies as well as disruption of actin bundles and impairment of focal adhesion formation. Y-27632 in addition inhibited Cch-induced contraction of isolated bovine CM strips.
CONCLUSIONS. Administration of Y-27632 caused a reduction in IOP and an increase in the outflow facility. The in vitro experiments suggest that the IOP-lowering effects of Y-27632 may be related to the altered cellular behavior of TM cells and relaxation of CM contraction. These studies suggest that ROCK inhibitors may have great potential to be developed for treatment of glaucoma and other ocular diseases.
This article has been cited by other articles:
|
|
 |
|
  H. Tanihara, M. Inatani, M. Honjo, H. Tokushige, J. Azuma, and M. Araie Intraocular Pressure-Lowering Effects and Safety of Topical Administration of a Selective ROCK Inhibitor, SNJ-1656, in Healthy Volunteers Arch Ophthalmol, March 1, 2008; 126(3): 309 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Kolavennu, L. Zeng, H. Peng, Y. Wang, and F. R. Danesh Targeting of RhoA/ROCK Signaling Ameliorates Progression of Diabetic Nephropathy Independent of Glucose Control Diabetes, March 1, 2008; 57(3): 714 - 723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Shen, T. Koga, B.-C. Park, N. SundarRaj, and B. Y. J. T. Yue Rho GTPase and cAMP/Protein Kinase A Signaling Mediates Myocilin-induced Alterations in Cultured Human Trabecular Meshwork Cells J. Biol. Chem., January 4, 2008; 283(1): 603 - 612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Schroter, D. Minond, A. Weiser, C. Dao, J. Habel, T. Spicer, P. Chase, P. Baillargeon, L. Scampavia, S. Schurer, et al. Comparison of Miniaturized Time-Resolved Fluorescence Resonance Energy Transfer and Enzyme-Coupled Luciferase High-Throughput Screening Assays to Discover Inhibitors of Rho-Kinase II (ROCK-II) J Biomol Screen, January 1, 2008; 13(1): 17 - 28. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Honjo, H. Tanihara, T. Kameda, T. Kawaji, N. Yoshimura, and M. Araie Potential Role of Rho-Associated Protein Kinase Inhibitor Y-27632 in Glaucoma Filtration Surgery Invest. Ophthalmol. Vis. Sci., December 1, 2007; 48(12): 5549 - 5557. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tokushige, M. Inatani, S. Nemoto, H. Sakaki, K. Katayama, M. Uehata, and H. Tanihara 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., July 1, 2007; 48(7): 3216 - 3222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sanka, R. Maddala, D. L. Epstein, and P. V. Rao Influence of Actin Cytoskeletal Integrity on Matrix Metalloproteinase-2 Activation in Cultured Human Trabecular Meshwork Cells Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2105 - 2114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tura, S. Grisanti, K. Petermeier, and S. Henke-Fahle The Rho-Kinase Inhibitor H-1152P Suppresses the Wound-Healing Activities of Human Tenon's Capsule Fibroblasts In Vitro Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2152 - 2161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Yuge, K. Nasu, H. Matsumoto, M. Nishida, and H. Narahara Collagen gel contractility is enhanced in human endometriotic stromal cells: a possible mechanism underlying the pathogenesis of endometriosis-associated fibrosis Hum. Reprod., April 1, 2007; 22(4): 938 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hasegawa, J. Nishimura, N. Niiro, K. Hirano, T. Ishibashi, and H. Kanaide Prostaglandin F2{alpha}, but Not Latanoprost, Increases the Ca2+ Sensitivity of the Pig Iris Sphincter Muscle Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4865 - 4871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Meyer-ter-Vehn, S. Sieprath, B. Katzenberger, S. Gebhardt, F. Grehn, and G. Schlunck Contractility as a Prerequisite for TGF-{beta}-Induced Myofibroblast Transdifferentiation in Human Tenon Fibroblasts Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4895 - 4904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Gonzalez Jr, J. A. Faralli, J. M. Peters, J. R. Newman, and D. M. Peters Effect of Heparin II Domain of Fibronectin on Actin Cytoskeleton and Adherens Junctions in Human Trabecular Meshwork Cells. Invest. Ophthalmol. Vis. Sci., July 1, 2006; 47(7): 2924 - 2931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Filla, A. Woods, P. L. Kaufman, and D. M. Peters {beta}1 and {beta}3 Integrins Cooperate to Induce Syndecan-4-Containing Cross-linked Actin Networks in Human Trabecular Meshwork Cells Invest. Ophthalmol. Vis. Sci., May 1, 2006; 47(5): 1956 - 1967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Noma, N. Oyama, and J. K. Liao Physiological role of ROCKs in the cardiovascular system Am J Physiol Cell Physiol, March 1, 2006; 290(3): C661 - C668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zhang and P. V. Rao Blebbistatin, a Novel Inhibitor of Myosin II ATPase Activity, Increases Aqueous Humor Outflow Facility in Perfused Enucleated Porcine Eyes Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 4130 - 4138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Song, P.-F. Deng, S. S. Stinnett, D. L. Epstein, and P. V. Rao Effects of Cholesterol-Lowering Statins on the Aqueous Humor Outflow Pathway Invest. Ophthalmol. Vis. Sci., July 1, 2005; 46(7): 2424 - 2432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zheng, H. Bando, Y. Ikuno, Y. Oshima, M. Sawa, M. Ohji, and Y. Tano Involvement of Rho-Kinase Pathway in Contractile Activity of Rabbit RPE Cells In Vivo and In Vitro Invest. Ophthalmol. Vis. Sci., February 1, 2004; 45(2): 668 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nakamura, T. Sagara, K. Seki, S. Hirano, and T. Nishida Permissive Effect of Fibronectin on Collagen Gel Contraction Mediated by Bovine Trabecular Meshwork Cells Invest. Ophthalmol. Vis. Sci., October 1, 2003; 44(10): 4331 - 4336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nakamura, S. Hirano, K. Suzuki, K. Seki, T. Sagara, and T. Nishida Signaling Mechanism of TGF-{beta}1-Induced Collagen Contraction Mediated by Bovine Trabecular Meshwork Cells Invest. Ophthalmol. Vis. Sci., November 1, 2002; 43(11): 3465 - 3472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tahara, K.-i. Morishige, K. Sawada, Y. Ikebuchi, R. Kawagishi, K. Tasaka, and Y. Murata RhoA/Rho-Kinase Cascade Is Involved in Oxytocin-Induced Rat Uterine Contraction Endocrinology, March 1, 2002; 143(3): 920 - 929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Honjo, M. Inatani, N. Kido, T. Sawamura, B. Y.-J. T. Yue, Y. Honda, and H. Tanihara Effects of Protein Kinase Inhibitor, HA1077, on Intraocular Pressure and Outflow Facility in Rabbit Eyes Arch Ophthalmol, August 1, 2001; 119(8): 1171 - 1178. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
