Calcium channel blockade reduces mechanical strain-induced extracellular matrix gene response in lamina cribrosa cells
PurposeThis study examines the effect of the L-type calcium channel blocker verapamil on mechanical strain-induced extracellular matrix genes in optic nerve head lamina cribrosa (LC) cells.MethodsChanges in LC cell intracellular calcium [Ca2+]i following hypotonic cell membrane stretch were measured...
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| Veröffentlicht in: | British journal of ophthalmology 2015-07, Vol.99 (7), p.1009-1014 |
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| creator | Quill, B Irnaten, M Docherty, N G McElnea, E M Wallace, D M Clark, A F O'Brien, C J |
| description | PurposeThis study examines the effect of the L-type calcium channel blocker verapamil on mechanical strain-induced extracellular matrix genes in optic nerve head lamina cribrosa (LC) cells.MethodsChanges in LC cell intracellular calcium [Ca2+]i following hypotonic cell membrane stretch were measured with the fluorescent probe fura-2/AM. Fluorescence intensity was measured, after labelling, by calcium (Ca2+) imaging confocal microscopy. Confluent human LC cell cultures were serum starved for 24 h prior to exposure to cyclical mechanical strain (1 Hz, 15%) for 24 h in the presence or absence of verapamil (10 mm). Transforming growth factor-β 1 (TGF-β1), collagen 6A3 (COL6A3) and chondroitin sulfate proteoglycan 2 (CSPG2) mRNA expression levels were assessed by quantitative RT-PCR.ResultsHypotonic cell membrane stretch of LC cells from normal donors significantly increased [Ca2+]i (p |
| doi_str_mv | 10.1136/bjophthalmol-2014-306093 |
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Fluorescence intensity was measured, after labelling, by calcium (Ca2+) imaging confocal microscopy. Confluent human LC cell cultures were serum starved for 24 h prior to exposure to cyclical mechanical strain (1 Hz, 15%) for 24 h in the presence or absence of verapamil (10 mm). Transforming growth factor-β 1 (TGF-β1), collagen 6A3 (COL6A3) and chondroitin sulfate proteoglycan 2 (CSPG2) mRNA expression levels were assessed by quantitative RT-PCR.ResultsHypotonic cell membrane stretch of LC cells from normal donors significantly increased [Ca2+]i (p<0.05). Exposure to cyclical mechanical strain (15% strain) produced a statistically significant increase in the three matrix genes that were examined (TGF-β1, COL6A3 and CSPG2). This response in both cyclical and mechanical stretch was significantly reduced by pretreating LC cells with the L-type calcium channel blocker verapamil (p<0.05).ConclusionsThis study provides evidence of a novel mechanotransduction pathway linking mechanical strain, cation channel function and the induction of LC cell matrix gene transcription. This highlights the potential involvement of calcium influx in the activation of matrix remodelling responses in the optic nerve head and supports the rationale that calcium channel blockers may attenuate disease progression in glaucoma.</description><identifier>ISSN: 0007-1161</identifier><identifier>EISSN: 1468-2079</identifier><identifier>DOI: 10.1136/bjophthalmol-2014-306093</identifier><identifier>PMID: 25795916</identifier><identifier>CODEN: BJOPAL</identifier><language>eng</language><publisher>England: BMJ Publishing Group LTD</publisher><subject>Aged ; Aged, 80 and over ; Apoptosis ; Calcium ; Calcium - metabolism ; Calcium Channel Blockers - pharmacology ; Calcium Channels, L-Type - physiology ; Cells, Cultured ; Collagen Type VI - genetics ; Extracellular matrix ; Extracellular Matrix - genetics ; Fura-2 - analogs & derivatives ; Fura-2 - metabolism ; Gene expression ; Gene Expression Regulation - physiology ; Glaucoma ; Humans ; Mechanotransduction, Cellular - drug effects ; Mechanotransduction, Cellular - physiology ; Microscopy, Confocal ; Optic Disk - cytology ; Optic nerve ; Pathology ; Real-Time Polymerase Chain Reaction ; RNA, Messenger - genetics ; Stem cells ; Stress, Mechanical ; Transforming Growth Factor beta1 - genetics ; Verapamil - pharmacology ; Versicans - genetics</subject><ispartof>British journal of ophthalmology, 2015-07, Vol.99 (7), p.1009-1014</ispartof><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</rights><rights>Copyright: 2015 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b470t-d4c3e0196cd24c40e71e05280c401ca715c05f5aaa729a1ff9e9e49227b1c0a83</citedby><cites>FETCH-LOGICAL-b470t-d4c3e0196cd24c40e71e05280c401ca715c05f5aaa729a1ff9e9e49227b1c0a83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://bjo.bmj.com/content/99/7/1009.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://bjo.bmj.com/content/99/7/1009.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,314,780,784,3196,23571,27924,27925,77600,77631</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25795916$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Quill, B</creatorcontrib><creatorcontrib>Irnaten, M</creatorcontrib><creatorcontrib>Docherty, N G</creatorcontrib><creatorcontrib>McElnea, E M</creatorcontrib><creatorcontrib>Wallace, D M</creatorcontrib><creatorcontrib>Clark, A F</creatorcontrib><creatorcontrib>O'Brien, C J</creatorcontrib><title>Calcium channel blockade reduces mechanical strain-induced extracellular matrix gene response in lamina cribrosa cells</title><title>British journal of ophthalmology</title><addtitle>Br J Ophthalmol</addtitle><description>PurposeThis study examines the effect of the L-type calcium channel blocker verapamil on mechanical strain-induced extracellular matrix genes in optic nerve head lamina cribrosa (LC) cells.MethodsChanges in LC cell intracellular calcium [Ca2+]i following hypotonic cell membrane stretch were measured with the fluorescent probe fura-2/AM. Fluorescence intensity was measured, after labelling, by calcium (Ca2+) imaging confocal microscopy. Confluent human LC cell cultures were serum starved for 24 h prior to exposure to cyclical mechanical strain (1 Hz, 15%) for 24 h in the presence or absence of verapamil (10 mm). Transforming growth factor-β 1 (TGF-β1), collagen 6A3 (COL6A3) and chondroitin sulfate proteoglycan 2 (CSPG2) mRNA expression levels were assessed by quantitative RT-PCR.ResultsHypotonic cell membrane stretch of LC cells from normal donors significantly increased [Ca2+]i (p<0.05). Exposure to cyclical mechanical strain (15% strain) produced a statistically significant increase in the three matrix genes that were examined (TGF-β1, COL6A3 and CSPG2). This response in both cyclical and mechanical stretch was significantly reduced by pretreating LC cells with the L-type calcium channel blocker verapamil (p<0.05).ConclusionsThis study provides evidence of a novel mechanotransduction pathway linking mechanical strain, cation channel function and the induction of LC cell matrix gene transcription. This highlights the potential involvement of calcium influx in the activation of matrix remodelling responses in the optic nerve head and supports the rationale that calcium channel blockers may attenuate disease progression in glaucoma.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Apoptosis</subject><subject>Calcium</subject><subject>Calcium - metabolism</subject><subject>Calcium Channel Blockers - pharmacology</subject><subject>Calcium Channels, L-Type - physiology</subject><subject>Cells, Cultured</subject><subject>Collagen Type VI - genetics</subject><subject>Extracellular matrix</subject><subject>Extracellular Matrix - genetics</subject><subject>Fura-2 - analogs & derivatives</subject><subject>Fura-2 - metabolism</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - physiology</subject><subject>Glaucoma</subject><subject>Humans</subject><subject>Mechanotransduction, Cellular - drug effects</subject><subject>Mechanotransduction, Cellular - physiology</subject><subject>Microscopy, Confocal</subject><subject>Optic Disk - cytology</subject><subject>Optic nerve</subject><subject>Pathology</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>Stem cells</subject><subject>Stress, Mechanical</subject><subject>Transforming Growth Factor beta1 - genetics</subject><subject>Verapamil - pharmacology</subject><subject>Versicans - genetics</subject><issn>0007-1161</issn><issn>1468-2079</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkcFu1DAQhi0EotvCKyBLXLikeJzEjo9oBbRSJS70bE2cCevFcRY7Qe3b42gLQpw4zYzn-8cz-hnjIK4BavW-P86nw3LAMM2hkgKaqhZKmPoZ20GjuvKkzXO2E0LoCkDBBbvM-VhKqUC_ZBey1aY1oHbs5x6D8-vE3QFjpMD7MLvvOBBPNKyOMp9oa3mHgecloY-Vj1tn4PRQakchrAETn3BJ_oF_o7hp82mOmbiPPODkI3KXfJ_mXJIiyK_YixFDptdP8Yrdf_r4dX9T3X35fLv_cFf1jRZLNTSuJgFGuUE2rhGkgUQrO1FycKihdaIdW0TU0iCMoyFDjZFS9-AEdvUVe3eee0rzj5XyYieftw0w0rxmC8qAgFaYDX37D3qc1xTLdha07owCWatCdWfKlWNyotGekp8wPVoQdvPG_u2N3byxZ2-K9M3TB2s_0fBH-NuMAtRnoJ-O_z_2F00XoNY</recordid><startdate>20150701</startdate><enddate>20150701</enddate><creator>Quill, B</creator><creator>Irnaten, M</creator><creator>Docherty, N G</creator><creator>McElnea, E M</creator><creator>Wallace, D M</creator><creator>Clark, A F</creator><creator>O'Brien, C J</creator><general>BMJ Publishing Group LTD</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20150701</creationdate><title>Calcium channel blockade reduces mechanical strain-induced extracellular matrix gene response in lamina cribrosa cells</title><author>Quill, B ; Irnaten, M ; Docherty, N G ; McElnea, E M ; Wallace, D M ; Clark, A F ; O'Brien, C J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b470t-d4c3e0196cd24c40e71e05280c401ca715c05f5aaa729a1ff9e9e49227b1c0a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Apoptosis</topic><topic>Calcium</topic><topic>Calcium - metabolism</topic><topic>Calcium Channel Blockers - pharmacology</topic><topic>Calcium Channels, L-Type - physiology</topic><topic>Cells, Cultured</topic><topic>Collagen Type VI - genetics</topic><topic>Extracellular matrix</topic><topic>Extracellular Matrix - genetics</topic><topic>Fura-2 - analogs & derivatives</topic><topic>Fura-2 - metabolism</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - physiology</topic><topic>Glaucoma</topic><topic>Humans</topic><topic>Mechanotransduction, Cellular - drug effects</topic><topic>Mechanotransduction, Cellular - physiology</topic><topic>Microscopy, Confocal</topic><topic>Optic Disk - cytology</topic><topic>Optic nerve</topic><topic>Pathology</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>Stem cells</topic><topic>Stress, Mechanical</topic><topic>Transforming Growth Factor beta1 - genetics</topic><topic>Verapamil - pharmacology</topic><topic>Versicans - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Quill, B</creatorcontrib><creatorcontrib>Irnaten, M</creatorcontrib><creatorcontrib>Docherty, N G</creatorcontrib><creatorcontrib>McElnea, E M</creatorcontrib><creatorcontrib>Wallace, D M</creatorcontrib><creatorcontrib>Clark, A F</creatorcontrib><creatorcontrib>O'Brien, C J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of ophthalmology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Quill, B</au><au>Irnaten, M</au><au>Docherty, N G</au><au>McElnea, E M</au><au>Wallace, D M</au><au>Clark, A F</au><au>O'Brien, C J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Calcium channel blockade reduces mechanical strain-induced extracellular matrix gene response in lamina cribrosa cells</atitle><jtitle>British journal of ophthalmology</jtitle><addtitle>Br J Ophthalmol</addtitle><date>2015-07-01</date><risdate>2015</risdate><volume>99</volume><issue>7</issue><spage>1009</spage><epage>1014</epage><pages>1009-1014</pages><issn>0007-1161</issn><eissn>1468-2079</eissn><coden>BJOPAL</coden><abstract>PurposeThis study examines the effect of the L-type calcium channel blocker verapamil on mechanical strain-induced extracellular matrix genes in optic nerve head lamina cribrosa (LC) cells.MethodsChanges in LC cell intracellular calcium [Ca2+]i following hypotonic cell membrane stretch were measured with the fluorescent probe fura-2/AM. Fluorescence intensity was measured, after labelling, by calcium (Ca2+) imaging confocal microscopy. Confluent human LC cell cultures were serum starved for 24 h prior to exposure to cyclical mechanical strain (1 Hz, 15%) for 24 h in the presence or absence of verapamil (10 mm). Transforming growth factor-β 1 (TGF-β1), collagen 6A3 (COL6A3) and chondroitin sulfate proteoglycan 2 (CSPG2) mRNA expression levels were assessed by quantitative RT-PCR.ResultsHypotonic cell membrane stretch of LC cells from normal donors significantly increased [Ca2+]i (p<0.05). Exposure to cyclical mechanical strain (15% strain) produced a statistically significant increase in the three matrix genes that were examined (TGF-β1, COL6A3 and CSPG2). This response in both cyclical and mechanical stretch was significantly reduced by pretreating LC cells with the L-type calcium channel blocker verapamil (p<0.05).ConclusionsThis study provides evidence of a novel mechanotransduction pathway linking mechanical strain, cation channel function and the induction of LC cell matrix gene transcription. This highlights the potential involvement of calcium influx in the activation of matrix remodelling responses in the optic nerve head and supports the rationale that calcium channel blockers may attenuate disease progression in glaucoma.</abstract><cop>England</cop><pub>BMJ Publishing Group LTD</pub><pmid>25795916</pmid><doi>10.1136/bjophthalmol-2014-306093</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Aged, 80 and over Apoptosis Calcium Calcium - metabolism Calcium Channel Blockers - pharmacology Calcium Channels, L-Type - physiology Cells, Cultured Collagen Type VI - genetics Extracellular matrix Extracellular Matrix - genetics Fura-2 - analogs & derivatives Fura-2 - metabolism Gene expression Gene Expression Regulation - physiology Glaucoma Humans Mechanotransduction, Cellular - drug effects Mechanotransduction, Cellular - physiology Microscopy, Confocal Optic Disk - cytology Optic nerve Pathology Real-Time Polymerase Chain Reaction RNA, Messenger - genetics Stem cells Stress, Mechanical Transforming Growth Factor beta1 - genetics Verapamil - pharmacology Versicans - genetics |
| title | Calcium channel blockade reduces mechanical strain-induced extracellular matrix gene response in lamina cribrosa cells |
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