{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:14:13Z","timestamp":1791317653489,"version":"4.3.1"},"reference-count":84,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UK and Eire Glaucoma Society"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Purpose: Glaucoma, one of the leading causes of irreversible blindness, is a common progressive optic neuropathy characterised by visual field defects and structural changes to the optic nerve head (ONH). There is extracellular matrix (ECM) accumulation and fibrosis of the lamina cribrosa (LC) in the ONH, and consequently increased tissue stiffness of the LC connective tissue. Integrins are cell surface proteins that provide the key molecular link connecting cells to the ECM and serve as bidirectional sensors transmitting signals between cells and their environment to promote cell adhesion, proliferation, and remodelling of the ECM. Here, we investigated the expression of \u03b1V\u03b23 integrin in glaucoma LC cell, and its effect on stiffness-induced ECM gene transcription and cellular proliferation rate in normal (NLC) and glaucoma (GLC) LC cells, by down-regulating \u03b1V\u03b23 integrin expression using cilengitide (a known potent \u03b1V\u03b23 and \u03b1V\u03b25 inhibitor) and \u03b23 integrin siRNA knockdown. Methods: GLC cells were compared to age-matched controls NLC to determine differential expression levels of \u03b1V\u03b23 integrin, ECM genes (Col1A1, \u03b1-SMA, fibronectin, vitronectin), and proliferation rates. The effects of \u03b1V\u03b23 integrin blockade (with cilengitide) and silencing (with a pool of four predesigned \u03b1V\u03b23 integrin siRNAs) on ECM gene expression and proliferation rates were evaluated using both reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting in the human NLC cells cultured on soft (4 kPa) and stiff (100 kPa) substrate and in GLC cells grown on standard plastic plates. Results: \u03b1V\u03b23 integrin gene and protein expression were enhanced (p &lt; 0.05) in GLC cells as compared to NLC. Both cilengitide and siRNA significantly reduced \u03b1V\u03b23 expression in GLC. When NLC were grown in the stiff substrate, cilengitide and siRNA also significantly reduced the increased expression in \u03b1V\u03b23, ECM components, and proliferation rate. Conclusions: Here, we provide evidence of cilengitide- and siRNA-mediated silencing of \u03b1V\u03b23 integrin expression, and inhibition of ECM synthesis in LC cells. Therefore, \u03b1V\u03b23 integrin may be a promising target for the development of novel anti-fibrotic therapies for treating the LC cupping of the ONH in glaucoma.<\/jats:p>","DOI":"10.3390\/cells13171487","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T02:34:06Z","timestamp":1725503646000},"page":"1487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Role of \u03b1v\u03b23 Integrin in Lamina Cribrosa Cell Mechanotransduction in Glaucoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Mustapha","family":"Irnaten","sequence":"first","affiliation":[{"name":"Clinical Research Centre, School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Gaynor","sequence":"additional","affiliation":[{"name":"Clinical Research Centre, School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colm","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Clinical Research Centre, School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland"},{"name":"Department of Ophthalmology, Mater Misericordiae University Hospital, D07 R2WY Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"Quigley","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.ophtha.2014.05.013","article-title":"Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis","volume":"121","author":"Tham","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1001\/archopht.1994.01090170088028","article-title":"Risk factors for the development of glaucomatous visual field loss in ocular hypertension","volume":"112","author":"Quigley","year":"1994","journal-title":"Arch. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.4137\/OED.S4909","article-title":"Clinical Options for the Reduction of Elevated Intraocular Pressure","volume":"4","author":"Crawley","year":"2012","journal-title":"Ophthalmol. Eye Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.ajo.2013.05.027","article-title":"Lifetime Risk of Blindness in Open-Angle Glaucoma","volume":"156","author":"Peters","year":"2013","journal-title":"Am. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/0002-9394(83)90389-6","article-title":"Morphologic Changes in the Lamina Cribrosa Correlated with Neural Loss in Open-Angle Glaucoma","volume":"95","author":"Quigley","year":"1983","journal-title":"Am. J. Ophthalmol."},{"key":"ref_7","first-page":"126","article-title":"Chronic experimental glaucoma in primates. I. Production of elevated intraocular pressure by anterior chamber injection of autologous ghost red blood cells","volume":"19","author":"Quigley","year":"1980","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/OPX.0b013e31817841cb","article-title":"Mechanical environment of the optic nerve head in glaucoma","volume":"85","author":"Downs","year":"2008","journal-title":"Optom. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1136\/bjo.84.3.318","article-title":"Age related compliance of the lamina cribrosa in human eyes","volume":"84","author":"Albon","year":"2000","journal-title":"Br. J. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1136\/bjo.79.4.368","article-title":"Changes in the collagenous matrix of the aging human lamina cribrosa","volume":"79","author":"Albon","year":"1995","journal-title":"Br. J. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.preteyeres.2004.06.001","article-title":"The optic nerve head as a biomechanical structure: A new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage","volume":"24","author":"Burgoyne","year":"2005","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"C611","DOI":"10.1152\/ajpcell.00054.2020","article-title":"The role of lamina cribrosa tissue stiffness and fibrosis as fundamental biomechanical drivers of pathological glaucoma cupping","volume":"319","author":"Hopkins","year":"2020","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1001\/archopht.1989.01070020298042","article-title":"The Relation Between Glaucomatous Damage and Optic Nerve Head Mechanical Compliance","volume":"107","author":"Zeimer","year":"1989","journal-title":"Arch. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1001\/archopht.1994.01090140137035","article-title":"Global and regional detection of induced optic disc change by digitised image analysis","volume":"112","author":"Burgoyne","year":"1994","journal-title":"Arch. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1016\/S0161-6420(95)30792-0","article-title":"Measurement of optic disc compliance by digitised image analysis in the normal monkey eye","volume":"102","author":"Burgoyne","year":"1995","journal-title":"Ophthalmology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1016\/S0161-6420(95)30791-9","article-title":"Early changes in optic disc compliance and surface position in experimental glaucoma","volume":"102","author":"Burgoyne","year":"1995","journal-title":"Ophthalmology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0161-6420(91)32345-5","article-title":"Displacement of the optic nerve head by acute changes in intraocular pressure in monkey eyes","volume":"98","author":"Coleman","year":"1991","journal-title":"Ophthalmology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0002-9394(14)75984-7","article-title":"Changes in the extracellular matrix of the human optic nerve head in primary open-angle glaucoma","volume":"109","author":"Hernandez","year":"1990","journal-title":"Am. J. Ophthalmol."},{"key":"ref_19","first-page":"78","article-title":"Cell culture of the human lamina cribrosa","volume":"29","author":"Hernandez","year":"1988","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1167\/iovs.10-6342","article-title":"Elastic Modulus Determination of Normal and Glaucomatous Human Trabecular Meshwork","volume":"52","author":"Last","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4809","DOI":"10.1167\/iovs.17-22175","article-title":"Estimating Human Trabecular Meshwork Stiffness by Numerical Modeling and Advanced OCT Imaging","volume":"58","author":"Wang","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.exer.2016.07.011","article-title":"Trabecular meshwork stiffness in glaucoma","volume":"158","author":"Wang","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_23","first-page":"76","article-title":"Induction of vitronectin and integrin \u03b1v in the retina after optic nerve injury","volume":"12","author":"Wang","year":"2006","journal-title":"Mol. Vis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26555","DOI":"10.1073\/pnas.1911837116","article-title":"Increased stiffness and flow resistance of the inner wall of Schlemm\u2019s canal in glaucomatous human eyes","volume":"116","author":"Vahabikashi","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1242\/jcs.03098","article-title":"Integrin ligands at a glance","volume":"119","author":"Humphries","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s00441-009-0834-6","article-title":"Integrins","volume":"339","author":"Malgorzata","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.tcb.2014.12.006","article-title":"Integrins and cancer: Regulators of cancer stemness, metastasis, and drug resistance","volume":"25","author":"Seguin","year":"2015","journal-title":"Trends Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1152\/jappl.2001.91.2.963","article-title":"Invited Review: Focal adhesion and small heat shock proteins in the regulation of actin remodeling and contractility in smooth muscle","volume":"91","author":"Gerthoffer","year":"2001","journal-title":"J. Appl. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0092-8674(02)00971-6","article-title":"Integrins: Bidirectional, Allosteric Signaling Machines","volume":"110","author":"Hynes","year":"2002","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s00441-016-2407-9","article-title":"\u03b1v integrins: Key regulators of tissue fibrosis","volume":"365","author":"Conroy","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Campbell, I.D., and Humphries, M.J. (2011). Integrin structure, activation, and interactions. Cold Spring Harb. Perspect. Biol., 3.","DOI":"10.1101\/cshperspect.a004994"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1183\/09059180.00010909","article-title":"The role of integrins in pulmonary fibrosis","volume":"17","author":"Sheppard","year":"2008","journal-title":"Eur. Respir. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.bbadis.2012.10.005","article-title":"Integrin-mediated regulation of TGF\u03b2 in fibrosis","volume":"1832","author":"Henderson","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_34","first-page":"G425","article-title":"Role of integrins in fibrosing liver diseases","volume":"301","author":"Patsenker","year":"2011","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e97597","DOI":"10.1172\/jci.insight.97597","article-title":"\u03b1v\u03b23 Integrin drives fibroblast contraction and strain stiffening of soft provisional matrix during progressive fibrosis","volume":"3","author":"Fiore","year":"2018","journal-title":"JCI Insight"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1089\/wound.2013.0436","article-title":"Integrins in wound healing","volume":"3","author":"Koivisto","year":"2014","journal-title":"Adv. Wound Care"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Filla, M.S., Meyer, K.K., Faralli, J.A., and Peters, D.M. (2021). Overexpression and Activation of \u03b1v\u03b23 Integrin Differentially Affects TGF\u03b22 Signaling in Human Trabecular Meshwork Cells. Cells, 10.","DOI":"10.3390\/cells10081923"},{"key":"ref_38","first-page":"453","article-title":"Integrins in the optic nerve head: Potential roles in glaucomatous optic neuropathy (an American Ophthalmological Society thesis)","volume":"104","author":"Morrison","year":"2006","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.exer.2017.02.010","article-title":"Cross-linked actin networks (CLANs) in glaucoma","volume":"159","author":"Bermudez","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1167\/iovs.05-0626","article-title":"\u03b21 and \u03b23 integrins cooperate to induce syndecan-4-containing cross-linked actin networks in human trabecular meshwork cells","volume":"47","author":"Filla","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.exer.2016.05.011","article-title":"The role of integrins in glaucoma","volume":"158","author":"Filla","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17409","DOI":"10.1016\/S0021-9258(18)41941-2","article-title":"Transforming growth factor beta differentially regulates expression of integrin subunits in guinea pig airway epithelial cells","volume":"267","author":"Sheppard","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1089\/jop.2013.0176","article-title":"The Role of Integrins in the Trabecular Meshwork","volume":"30","author":"Gagen","year":"2013","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.ejcb.2011.03.005","article-title":"Overexpression of osteopontin induces angiogenesis of endothelial progenitor cells via the av\u03b23\/PI3K\/AKT\/eNOS\/NO signaling pathway in glioma cells","volume":"90","author":"Wang","year":"2011","journal-title":"Eur. J. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"C205","DOI":"10.1152\/ajpcell.00347.2014","article-title":"Role of nitric oxide in murine conventional outflow physiology","volume":"309","author":"Chang","year":"2015","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.1016\/j.bbamcr.2013.09.020","article-title":"Dexamethasone increases \u03b1v\u03b23 integrin expression and affinity through a calcineurin\/NFAT pathway","volume":"1833","author":"Faralli","year":"2013","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.1093\/emboj\/20.17.4639","article-title":"Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment","volume":"20","author":"Tzima","year":"2001","journal-title":"EMBO J."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Schwarzbauer, J.E., and DeSimone, D.W. (2011). Fibronectins, their fibrillogenesis, and in vivo functions. Cold Spring Harb. Perspect. Biol., 3.","DOI":"10.1101\/cshperspect.a005041"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/glia.20247","article-title":"Transforming Growth factor-\u03b2-regulated gene transcription and protein expression in human GFAP-negative lamina cribrosa cells","volume":"52","author":"Kirwan","year":"2005","journal-title":"Glia"},{"key":"ref_50","first-page":"1182","article-title":"Oxidative stress, mitochondrial dysfunction and calcium overload in human lamina cribrosa cells from glaucoma donors","volume":"17","author":"McElnea","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_51","first-page":"76","article-title":"Differential global and extra-cellular matrix focused gene expression patterns between normal and glaucomatous human lamina cribrosa cells","volume":"15","author":"Kirwan","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1167\/iovs.17-22400","article-title":"Increased substrate stiffness elicits a myofibroblastic phenotype in human lamina cribrosa cells","volume":"59","author":"Liu","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"108103","DOI":"10.1016\/j.exer.2020.108103","article-title":"Isolation and characterization of human optic nerve head astrocytes and lamina cribrosa cells","volume":"197","author":"Lopez","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Lambert, W.S., Clark, A.F., and Wordinger, R.J. (2004). Neurotrophin and Trk expression by cells of the human lamina cribrosa following oxygen-glucose deprivation. BMC Neurosci., 5.","DOI":"10.1186\/1471-2202-5-51"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1167\/iovs.17-22531","article-title":"Activation of the NFAT-calcium signaling pathway in human lamina cribrosa cells in glaucoma","volume":"59","author":"Irnaten","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1021\/jm0102598","article-title":"Nanomolar small molecule inhibitors for \u03b1v\u03b26, \u03b1v\u03b25, and \u03b1v\u03b23 integrins","volume":"45","author":"Goodman","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1097\/IJG.0000000000000627","article-title":"Targeting Transforming Growth Factor-\u03b2 Signaling in Primary Open-Angle Glaucoma","volume":"26","author":"Wang","year":"2017","journal-title":"J. Glaucoma"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/0955-0674(92)90100-Q","article-title":"Signal transduction by integrin receptors for extracellular matrix: Cooperative processing of extracellular information","volume":"4","author":"Damsky","year":"1992","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3897","DOI":"10.1167\/iovs.19-27171","article-title":"Activation of \u03b1v\u03b23 integrin alters fibronectin fibril formation in human trabecular meshwork cells in a ROCK-independent manner","volume":"60","author":"Filla","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1136\/bjo.83.2.209","article-title":"Transforming growth factor beta isoforms in human optic nerve heads","volume":"83","author":"Pena","year":"1999","journal-title":"Br. J. Ophthalmol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.matbio.2014.03.007","article-title":"The role of matricellular proteins in glaucoma","volume":"37","author":"Wallace","year":"2014","journal-title":"Matrix Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.2353\/ajpath.2009.090393","article-title":"Integrin-mediated transforming growth factor-beta activation, a potential therapeutic target in fibrogenic disorders","volume":"175","author":"Nishimura","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Brown, N.F., and Marshall, J.F. (2019). Integrin-Mediated TGF\u03b2 Activation Modulates the Tumour Microenvironment. Cancers, 11.","DOI":"10.3390\/cancers11091221"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1167\/iovs.18-26038","article-title":"Effect of \u03b1v\u03b23 integrin expression and activity on intraocular pressure","volume":"60","author":"Faralli","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/j.1749-6632.1999.tb07996.x","article-title":"Matrix remodeling after stroke. De novo expression of matrix proteins and integrin receptors","volume":"890","author":"Ellison","year":"1999","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/S0960-9822(01)00262-7","article-title":"Thy-1 binds to integrin \u03b23 on astrocytes and triggers formation of focal contact sites","volume":"11","author":"Leyton","year":"2001","journal-title":"Curr. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/biof.41","article-title":"Roles and regulation of Thy-1, a context dependent modulator of cell phenotype","volume":"35","author":"Bradley","year":"2009","journal-title":"Biofactors"},{"key":"ref_69","first-page":"192","article-title":"Changes in Thy1 gene expression associated with damaged retinal ganglion cells","volume":"7","author":"Schlamp","year":"2001","journal-title":"Mol. Vis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.bbamcr.2008.01.034","article-title":"Direct Thy-1\/\u03b1V\u03b23 integrin interaction mediates neuron to astrocyte communication","volume":"1783","author":"Hermosilla","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1242\/jcs.073171","article-title":"ATP release due to Thy-1-integrin binding induces P2X7-mediated calcium entry required for focal adhesion formation","volume":"124","author":"Valdivia","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Herrera-Molina, R., Frischknecht, R., Maldonado, H., Seidenbecher, C.I., Gundelfinger, E.D., Hetz, C., Aylwin Mde, L., Schneider, P., Quest, A.F., and Leyton, L. (2012). Astrocytic \u03b1V\u03b23 integrin inhibits neurite outgrowth and promotes retraction of neuronal processes by clustering Thy-1. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034295"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Lagos-Cabr\u00e9, R., Brenet, M., D\u00edaz, J., P\u00e9rez, R.D., P\u00e9rez, L.A., Herrera-Molina, R., Quest, A.F.G., and Leyton, L. (2018). Intracellular Ca2+ increases and connexin 43 hemichannel opening are necessary but not sufficient for thy-1-induced astrocyte migration. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082179"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"108138","DOI":"10.1016\/j.exer.2020.108138","article-title":"Integrin: Basement membrane adhesion by corneal epithelial and endothelial cells","volume":"198","author":"McKay","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Ma\u0142gorzata, M., Bryl, A., Falkowski, M., and Zorena, K. (2021). Integrins: An Important Link between Angiogenesis, Inflammation and Eye Diseases. Cells, 10.","DOI":"10.3390\/cells10071703"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.exer.2018.11.027","article-title":"Initiation of fibrosis in the integrin Av\u03b26 knockout mice","volume":"180","author":"Wu","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.1167\/iovs.14-14154","article-title":"Extracellular matrix alterations in late-onset Fuchs\u2019 corneal dystrophy","volume":"55","author":"Weller","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e02019-16","DOI":"10.1128\/JVI.02019-16","article-title":"Human Adenovirus Type 37 Uses \u03b1V\u03b21 and \u03b13\u03b21 Integrins for Infection of Human Corneal Cells","volume":"91","author":"Storm","year":"2017","journal-title":"J. Virol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1186\/s12967-018-1730-1","article-title":"Integrin \u03b1\u03bd\u03b25 in vitro inhibition limits pro-fibrotic response in cardiac fibroblasts of spontaneously hypertensive rats","volume":"16","author":"Perrucci","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Bouvet, M., Claude, O., Roux, M., Skelly, D., Masurkar, N., Mougenot, N., Nadaud, S., Blanc, C., Delacroix, C., and Chardonnet, S. (2020). Anti-integrin \u03b1v therapy improves cardiac fibrosis after myocardial infarction by blunting cardiac PW1+ stromal cells. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-68223-8"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Balasubramanian, S., Quinones, L., Kasiganesan, H., Zhang, Y., Pleasant, D.L., Sundararaj, K.P., Zile, M.R., Bradshaw, A.D., and Kuppuswamy, D. (2012). \u03b23integrinin cardiac fibroblast is critical for extracellular matrix accumulation during pressure overload hypertrophy in mouse. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045076"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1093\/annonc\/mdm140","article-title":"Assessment of the biological and pharmacological effects of the \u03b1\u03bd\u03b23 and \u03b1\u03bd\u03b25 integrin receptor antagonist, cilengitide (EMD 121974), in patients with advanced solid tumors","volume":"18","author":"Hariharan","year":"2007","journal-title":"Ann. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1517\/13543784.17.8.1225","article-title":"Cilengitide: An integrin-targeting arginine-glycine-aspartic acid peptide with promising activity for glioblastoma multiforme","volume":"17","author":"Reardon","year":"2008","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.jhep.2006.11.011","article-title":"Pharmacological inhibition of the vitronectin receptor abrogates PDGF-BB-induced hepatic stellate cell migration and activation in vitro","volume":"46","author":"Patsenker","year":"2007","journal-title":"J. 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