Effects of Rho-Associated Protein Kinase Inhibitor Y-27632 on Intraocular Pressure and Outflow Facility
To elucidate the roles of Rho-associated protein kinase (ROCK) in regulating intraocular pressure (IOP) and outflow facility in the rabbit eye. 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...
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| Veröffentlicht in: | Investigative ophthalmology & visual science 2001-01, Vol.42 (1), p.137-144 |
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| creator | Honjo, Megumi Tanihara, Hidenobu Inatani, Masaru Kido, Noriaki Sawamura, Tatsuya Yue, Beatrice Y. J. T Narumiya, Shuh Honda, Yoshihito |
| description | To elucidate the roles of Rho-associated protein kinase (ROCK) in regulating intraocular pressure (IOP) and outflow facility in the rabbit eye.
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.
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.
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. |
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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.
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.
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.</description><identifier>ISSN: 0146-0404</identifier><identifier>EISSN: 1552-5783</identifier><identifier>PMID: 11133858</identifier><identifier>CODEN: IOVSDA</identifier><language>eng</language><publisher>Rockville, MD: ARVO</publisher><subject>Actins - metabolism ; Amides - pharmacology ; Animals ; Anterior Chamber - drug effects ; Anterior Chamber - metabolism ; Aqueous Humor - secretion ; Biological and medical sciences ; Blotting, Western ; Cells, Cultured ; Ciliary Body - metabolism ; Dose-Response Relationship, Drug ; Enzyme Inhibitors - pharmacology ; Eye ; Fluorescent Antibody Technique, Indirect ; Intracellular Signaling Peptides and Proteins ; Intraocular Pressure - drug effects ; Medical sciences ; Muscle Contraction - drug effects ; Muscle, Smooth - metabolism ; Pharmacology. Drug treatments ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Protein-Serine-Threonine Kinases - metabolism ; Pupil - drug effects ; Pyridines - pharmacology ; Rabbits ; rho-Associated Kinases ; Trabecular Meshwork - cytology ; Trabecular Meshwork - drug effects ; Trabecular Meshwork - metabolism ; Vinculin - metabolism</subject><ispartof>Investigative ophthalmology & visual science, 2001-01, Vol.42 (1), p.137-144</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=884605$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11133858$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Honjo, Megumi</creatorcontrib><creatorcontrib>Tanihara, Hidenobu</creatorcontrib><creatorcontrib>Inatani, Masaru</creatorcontrib><creatorcontrib>Kido, Noriaki</creatorcontrib><creatorcontrib>Sawamura, Tatsuya</creatorcontrib><creatorcontrib>Yue, Beatrice Y. J. T</creatorcontrib><creatorcontrib>Narumiya, Shuh</creatorcontrib><creatorcontrib>Honda, Yoshihito</creatorcontrib><title>Effects of Rho-Associated Protein Kinase Inhibitor Y-27632 on Intraocular Pressure and Outflow Facility</title><title>Investigative ophthalmology & visual science</title><addtitle>Invest Ophthalmol Vis Sci</addtitle><description>To elucidate the roles of Rho-associated protein kinase (ROCK) in regulating intraocular pressure (IOP) and outflow facility in the rabbit eye.
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.
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.
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.</description><subject>Actins - metabolism</subject><subject>Amides - pharmacology</subject><subject>Animals</subject><subject>Anterior Chamber - drug effects</subject><subject>Anterior Chamber - metabolism</subject><subject>Aqueous Humor - secretion</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Cells, Cultured</subject><subject>Ciliary Body - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Eye</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Intraocular Pressure - drug effects</subject><subject>Medical sciences</subject><subject>Muscle Contraction - drug effects</subject><subject>Muscle, Smooth - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Pupil - drug effects</subject><subject>Pyridines - pharmacology</subject><subject>Rabbits</subject><subject>rho-Associated Kinases</subject><subject>Trabecular Meshwork - cytology</subject><subject>Trabecular Meshwork - drug effects</subject><subject>Trabecular Meshwork - metabolism</subject><subject>Vinculin - metabolism</subject><issn>0146-0404</issn><issn>1552-5783</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo90E1LxDAQBuAiiq4ff0ECordC0iRN9yjLqouCInrwFKbp1EbSRpOU4r-3squngeHhnZfZyxZMyiKXquL72YIyUeZUUHGUHcf4QWnBWEEPsyPGGOeVrBbZ-7pt0aRIfEueO59fx-iNhYQNeQo-oR3IvR0gItkMna1t8oG85YUqeUH8MC9TAG9GB2H2GOMYkMDQkMcxtc5P5AaMdTZ9n2YHLbiIZ7t5kr3erF9Wd_nD4-1mdf2Qd0UpU740lDeAYKq5OlUtAqWoBLBlAzXltZSCGSwNZ6UyVCrRMOSVkKxWYilqyU-yq23uZ_BfI8akexsNOgcD-jFqRWXJKl7O8HwHx7rHRn8G20P41n-vmcHFDkA04NoAg7Hx31XVXPD33uVWdfa9m2xAHXtwbg5lepomUWimGVf8B1kaeUU</recordid><startdate>20010101</startdate><enddate>20010101</enddate><creator>Honjo, Megumi</creator><creator>Tanihara, Hidenobu</creator><creator>Inatani, Masaru</creator><creator>Kido, Noriaki</creator><creator>Sawamura, Tatsuya</creator><creator>Yue, Beatrice Y. J. T</creator><creator>Narumiya, Shuh</creator><creator>Honda, Yoshihito</creator><general>ARVO</general><general>Association for Research in Vision and Ophtalmology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20010101</creationdate><title>Effects of Rho-Associated Protein Kinase Inhibitor Y-27632 on Intraocular Pressure and Outflow Facility</title><author>Honjo, Megumi ; Tanihara, Hidenobu ; Inatani, Masaru ; Kido, Noriaki ; Sawamura, Tatsuya ; Yue, Beatrice Y. J. T ; Narumiya, Shuh ; Honda, Yoshihito</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h265t-9c03daeac814607fea00e74a19dab03b5541ce6c3167c0574d1e38451b7494b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Actins - metabolism</topic><topic>Amides - pharmacology</topic><topic>Animals</topic><topic>Anterior Chamber - drug effects</topic><topic>Anterior Chamber - metabolism</topic><topic>Aqueous Humor - secretion</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Cells, Cultured</topic><topic>Ciliary Body - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Eye</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Intraocular Pressure - drug effects</topic><topic>Medical sciences</topic><topic>Muscle Contraction - drug effects</topic><topic>Muscle, Smooth - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Pupil - drug effects</topic><topic>Pyridines - pharmacology</topic><topic>Rabbits</topic><topic>rho-Associated Kinases</topic><topic>Trabecular Meshwork - cytology</topic><topic>Trabecular Meshwork - drug effects</topic><topic>Trabecular Meshwork - metabolism</topic><topic>Vinculin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Honjo, Megumi</creatorcontrib><creatorcontrib>Tanihara, Hidenobu</creatorcontrib><creatorcontrib>Inatani, Masaru</creatorcontrib><creatorcontrib>Kido, Noriaki</creatorcontrib><creatorcontrib>Sawamura, Tatsuya</creatorcontrib><creatorcontrib>Yue, Beatrice Y. J. T</creatorcontrib><creatorcontrib>Narumiya, Shuh</creatorcontrib><creatorcontrib>Honda, Yoshihito</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Investigative ophthalmology & visual science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Honjo, Megumi</au><au>Tanihara, Hidenobu</au><au>Inatani, Masaru</au><au>Kido, Noriaki</au><au>Sawamura, Tatsuya</au><au>Yue, Beatrice Y. J. T</au><au>Narumiya, Shuh</au><au>Honda, Yoshihito</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Rho-Associated Protein Kinase Inhibitor Y-27632 on Intraocular Pressure and Outflow Facility</atitle><jtitle>Investigative ophthalmology & visual science</jtitle><addtitle>Invest Ophthalmol Vis Sci</addtitle><date>2001-01-01</date><risdate>2001</risdate><volume>42</volume><issue>1</issue><spage>137</spage><epage>144</epage><pages>137-144</pages><issn>0146-0404</issn><eissn>1552-5783</eissn><coden>IOVSDA</coden><abstract>To elucidate the roles of Rho-associated protein kinase (ROCK) in regulating intraocular pressure (IOP) and outflow facility in the rabbit eye.
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.
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.
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.</abstract><cop>Rockville, MD</cop><pub>ARVO</pub><pmid>11133858</pmid><tpages>8</tpages></addata></record> |
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| ispartof | Investigative ophthalmology & visual science, 2001-01, Vol.42 (1), p.137-144 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Actins - metabolism Amides - pharmacology Animals Anterior Chamber - drug effects Anterior Chamber - metabolism Aqueous Humor - secretion Biological and medical sciences Blotting, Western Cells, Cultured Ciliary Body - metabolism Dose-Response Relationship, Drug Enzyme Inhibitors - pharmacology Eye Fluorescent Antibody Technique, Indirect Intracellular Signaling Peptides and Proteins Intraocular Pressure - drug effects Medical sciences Muscle Contraction - drug effects Muscle, Smooth - metabolism Pharmacology. Drug treatments Protein-Serine-Threonine Kinases - antagonists & inhibitors Protein-Serine-Threonine Kinases - metabolism Pupil - drug effects Pyridines - pharmacology Rabbits rho-Associated Kinases Trabecular Meshwork - cytology Trabecular Meshwork - drug effects Trabecular Meshwork - metabolism Vinculin - metabolism |
| title | Effects of Rho-Associated Protein Kinase Inhibitor Y-27632 on Intraocular Pressure and Outflow Facility |
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