{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:01:34Z","timestamp":1791928894679,"version":"4.3.4"},"reference-count":57,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"13","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2024,11,20]]},"DOI":"10.1167\/iovs.65.13.43","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T10:30:55Z","timestamp":1732098655000},"page":"43","source":"Crossref","is-referenced-by-count":8,"title":["The Mechanisms of Neuroprotection by Topical Rho Kinase Inhibition in Experimental Mouse Glaucoma and Optic Neuropathy"],"prefix":"10.1167","volume":"65","author":[{"given":"Sarah E.","family":"Quillen","sequence":"first","affiliation":[{"name":"Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C.","family":"Kimball","sequence":"additional","affiliation":[{"name":"Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey A.","family":"Ritter-Gordy","sequence":"additional","affiliation":[{"name":"Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Du","sequence":"additional","affiliation":[{"name":"Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuochen","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Pease","sequence":"additional","affiliation":[{"name":"Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salaheddine","family":"Madhoun","sequence":"additional","affiliation":[{"name":"Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thao D.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas V.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry A.","family":"Quigley","sequence":"additional","affiliation":[{"name":"Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian F.","family":"Pitha","sequence":"additional","affiliation":[{"name":"Glaucoma Center of Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"issue":"3","key":"bib1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.2165\/00063030-200721030-00004","article-title":"Rho GTPase\/Rho kinase inhibition as a novel target for the treatment of glaucoma","volume":"21","author":"Rao","year":"2007","journal-title":"BioDrugs"},{"issue":"8","key":"bib2","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1177\/1060028020971215","article-title":"Netarsudil for the treatment of open-angle glaucoma and ocular hypertension: a literature review","volume":"55","author":"Gonzalez","year":"2021","journal-title":"Ann Pharmacother"},{"issue":"3","key":"bib3","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1007\/s00417-021-05410-x","article-title":"The effectiveness and safety profile of netarsudil 0.02% in glaucoma treatment: real-world 6-month outcomes","volume":"260","author":"Shiuey","year":"2022","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"issue":"11","key":"bib4","doi-asserted-by":"publisher","first-page":"7126","DOI":"10.1167\/iovs.13-13842","article-title":"The novel Rho kinase (ROCK) inhibitor K-115: a new candidate drug for neuroprotective treatment in glaucoma","volume":"55","author":"Yamamoto","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib5","first-page":"15709","article-title":"Topical ripasudil stimulates neuroprotection and axon regeneration in adult mice following optic nerve injury","volume":"10","author":"Nishijima","year":"2020","journal-title":"Sci Reports"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.exer.2016.07.006","article-title":"Topical administration of a Rock\/Net inhibitor promotes retinal ganglion cell survival and axon regeneration after optic nerve injury","volume":"158","author":"Shaw","year":"2017","journal-title":"Exp Eye Res"},{"issue":"17","key":"bib7","doi-asserted-by":"publisher","first-page":"11745","DOI":"10.1021\/acs.jmedchem.2c00600","article-title":"Identification of nitric oxide-donating ripasudil derivatives with intraocular pressure lowering and retinal ganglion cell protection activities","volume":"65","author":"Yang","year":"2022","journal-title":"J Med Chem"},{"issue":"5(Special)","key":"bib8","first-page":"2431","article-title":"Fasudil protects retinal ganglion cells and promotes axonal regeneration","volume":"33","author":"Zhang","year":"2020","journal-title":"Pak J Pharm Sci"},{"issue":"1","key":"bib9","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1159\/000350138","article-title":"The neuroprotective potential of Rho-kinase inhibition in promoting cell survival and reducing reactive gliosis in response to hypoxia in isolated bovine retina","volume":"32","author":"Alt","year":"2013","journal-title":"Cell Physiol Biochem"},{"issue":"1","key":"bib10","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.nbd.2006.08.008","article-title":"Enhanced survival and regeneration of axotomized retinal neurons by repeated delivery of cell-permeable C3-like Rho antagonists","volume":"25","author":"Bertrand","year":"2007","journal-title":"Neurobiol Dis"},{"issue":"4","key":"bib11","doi-asserted-by":"publisher","first-page":"2264","DOI":"10.1167\/iovs.15-17411","article-title":"Vascular normalization by ROCK inhibitor: therapeutic potential of ripasudil (K-115) eye drop in retinal angiogenesis and hypoxia","volume":"57","author":"Yamaguchi","year":"2016","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"7","key":"bib12","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1089\/jop.2016.0028","article-title":"Ocular penetration and pharmacokinetics of ripasudil following topical administration to rabbits","volume":"32","author":"Isobe","year":"2016","journal-title":"J Ocul Pharmacol Ther"},{"issue":"1-2","key":"bib13","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1089\/jop.2017.0023","article-title":"Discovery and preclinical development of netarsudil, a novel ocular hypotensive agent for the treatment of glaucoma","volume":"34","author":"Lin","year":"2018","journal-title":"J Ocul Pharmacol Ther"},{"issue":"6","key":"bib14","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1167\/tvst.7.6.6","article-title":"Rho-kinase inhibition reduces myofibroblast differentiation and proliferation of scleral fibroblasts induced by transforming growth factor beta and experimental glaucoma","volume":"7","author":"Pitha","year":"2018","journal-title":"Transl Vis Sci Technol"},{"issue":"11","key":"bib15","doi-asserted-by":"publisher","first-page":"2609","DOI":"10.1002\/glia.24442","article-title":"The GPR84 molecule is a mediator of a subpopulation of retinal microglia that promote TNF\/IL-1alpha expression via the rho-ROCK pathway after optic nerve injury","volume":"71","author":"Sato","year":"2023","journal-title":"Glia"},{"issue":"9","key":"bib16","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1002\/cm.20472","article-title":"Rho-kinase\/ROCK: A key regulator of the cytoskeleton and cell polarity","volume":"67","author":"Amano","year":"2010","journal-title":"Cytoskeleton (Hoboken)"},{"issue":"2","key":"bib17","doi-asserted-by":"publisher","first-page":"272","DOI":"10.3390\/genes14020272","article-title":"Effect of the Rho-kinase\/ROCK signaling pathway on cytoskeleton components","volume":"14","author":"Guan","year":"2023","journal-title":"Genes (Basel)"},{"issue":"1","key":"bib18","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1007\/s00005-022-00642-z","article-title":"Rho kinases in embryonic development and stem cell research","volume":"70","author":"Shi","year":"2022","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"issue":"6","key":"bib19","doi-asserted-by":"publisher","first-page":"2269","DOI":"10.1021\/acs.jmedchem.5b00683","article-title":"Rho kinase (ROCK) inhibitors and their therapeutic potential","volume":"59","author":"Feng","year":"2016","journal-title":"J Med Chem"},{"issue":"6","key":"bib20","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1165\/rcmb.2016-0306OC","article-title":"Role of Rho-associated coiled-coil forming kinase isoforms in regulation of stiffness-induced myofibroblast differentiation in lung fibrosis","volume":"56","author":"Htwe","year":"2017","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"6","key":"bib21","doi-asserted-by":"crossref","first-page":"983","DOI":"10.4103\/1673-5374.184499","article-title":"Feng DX. ROCK inhibition enhances neurite outgrowth in neural stem cells by upregulating YAP expression in vitro","volume":"11","author":"Jia","year":"2016","journal-title":"Neural Regen Res"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/bs.pbr.2015.04.014","article-title":"Rho kinase inhibitor AMA0526 improves surgical outcome in a rabbit model of glaucoma filtration surgery","volume":"220","author":"Van de Velde","year":"2015","journal-title":"Prog Brain Res"},{"issue":"4","key":"bib23","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1124\/pr.115.010595","article-title":"Rho kinases in health and disease: from basic science to translational research","volume":"67","author":"Loirand","year":"2015","journal-title":"Pharmacol Rev"},{"issue":"1","key":"bib24","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.exer.2012.04.006","article-title":"The effects of anesthesia, mouse strain and age on intraocular pressure and an improved murine model of experimental glaucoma","volume":"99","author":"Cone","year":"2012","journal-title":"Exp Eye Res"},{"issue":"2","key":"bib25","doi-asserted-by":"publisher","first-page":"e0244123","DOI":"10.1371\/journal.pone.0244123","article-title":"The role of aquaporin-4 in optic nerve head astrocytes in experimental glaucoma","volume":"16","author":"Kimball","year":"2021","journal-title":"PLoS One"},{"issue":"1","key":"bib26","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1167\/iovs.09-3947","article-title":"The microbead occlusion model: a paradigm for induced ocular hypertension in rats and mice","volume":"51","author":"Sappington","year":"2010","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"108035","DOI":"10.1016\/j.exer.2020.108035","article-title":"A method to quantify regional axonal transport blockade at the optic nerve head after short term intraocular pressure elevation in mice","volume":"196","author":"Korneva","year":"2020","journal-title":"Exper Eye Res"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"109341","DOI":"10.1016\/j.exer.2022.109341","article-title":"Effects of experimental glaucoma in Lama1nmf223 mutant mice","volume":"226","author":"Madhoun","journal-title":"Exp Eye Res"},{"issue":"2","key":"bib29","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1167\/iovs.16-20620","article-title":"Measuring deformation in the mouse optic nerve head and peripapillary sclera","volume":"58","author":"Nguyen","year":"2017","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"1","key":"bib30","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s11340-014-9874-2","article-title":"A fast iterative digital volume correlation algorithm for large deformations","volume":"55","author":"Bar-Kochba","year":"2015","journal-title":"Exp Mech"},{"issue":"11","key":"bib31","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1167\/iovs.61.11.14","article-title":"Pressure-induced changes in astrocyte GFAP, actin, and nuclear morphology in mouse optic nerve","volume":"61","author":"Ling","year":"2020","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"10","key":"bib32","doi-asserted-by":"publisher","first-page":"4045","DOI":"10.1073\/pnas.1211284110","article-title":"Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death","volume":"110","author":"Welsbie","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"issue":"10","key":"bib33","doi-asserted-by":"publisher","first-page":"e0141137","DOI":"10.1371\/journal.pone.0141137","article-title":"Losartan treatment protects retinal ganglion cells and alters scleral remodeling in experimental glaucoma","volume":"10","author":"Quigley","year":"2015","journal-title":"PLoS One"},{"issue":"6","key":"bib34","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1007\/s11011-019-00487-0","article-title":"The Rho kinase inhibitor fasudil attenuates A\u00df1-42-induced apoptosis via the ASK1\/JNK signal pathway in primary cultures of hippocampal neurons","volume":"34","author":"Gao","year":"2019","journal-title":"Metab Brain Dis"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"276","DOI":"10.3389\/fphar.2015.00276","article-title":"The function of Rho-associated kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease","volume":"6","author":"Hartmann","year":"2015","journal-title":"Front. Pharmacol."},{"issue":"2","key":"bib36","first-page":"137","article-title":"Chronic experimental glaucoma in primates. II. Effect of extended intraocular pressure elevation on optic nerve head and axonal transport","volume":"19","author":"Quigley","year":"1980","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"15","key":"bib37","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1167\/iovs.64.15.14","article-title":"Comparison of the biomechanics of the mouse astrocytic lamina cribrosa between glaucoma and optic nerve crush models","volume":"64","author":"Korneva","year":"2023","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"10","key":"bib38","doi-asserted-by":"publisher","first-page":"2726","DOI":"10.3390\/cells10102726","article-title":"Cofilin and actin dynamics: multiple modes of regulation and their impacts in neuronal development and degeneration","volume":"10","author":"Bamburg","year":"2021","journal-title":"Cells"},{"issue":"7","key":"bib39","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1083\/jcb.147.7.1519","article-title":"Cofilin phosphorylation and actin cytoskeletal dynamics regulated by rho- and Cdc42-activated LIM-kinase 2","volume":"147","author":"Sumi","year":"1999","journal-title":"J Cell Biol"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"15817","DOI":"10.1038\/ncomms15817","article-title":"Optogenetic control of RhoA reveals zyxin mediated elasticity of stress fibres","volume":"8","author":"Oakes","year":"2017","journal-title":"Nat. Commun."},{"issue":"6","key":"bib41","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1083\/jcb.133.6.1403","article-title":"Rho-stimulated contractility drives the formation of stress fibers and focal adhesions","volume":"133","author":"Chrzanowska-Wodnicka","year":"1996","journal-title":"J Cell Biol"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"824","DOI":"10.3389\/fphys.2018.00824","article-title":"Cellular mechanotransduction: from tension to function","volume":"9","author":"Martino","year":"2018","journal-title":"Front Physiol."},{"issue":"1","key":"bib43","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.yexcr.2019.03.027","article-title":"Mechanical regulation of myofibroblast phenoconversion and collagen contraction","volume":"379","author":"Hinz","year":"2019","journal-title":"Exp Cell Res"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1080\/14656566.2017.1378344","article-title":"Ripasudil hydrochloride hydrate: targeting Rho kinase in the treatment of glaucoma","volume":"18","author":"Inoue","year":"2017","journal-title":"Expert Opin Pharmacother"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"50","DOI":"10.3389\/fnins.2015.00050","article-title":"Transcriptomic analysis, and 3D bioengineering of astrocytes indicate ROCK inhibition produces cytotrophic astrogliosis","volume":"9","author":"O'Shea","year":"2015","journal-title":"Front Neurosci"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"e0238104","DOI":"10.1371\/journal.pone.0238104","article-title":"Astrocyte responses to experimental glaucoma in mouse optic nerve head","volume":"15","author":"Quillen","year":"2020","journal-title":"PLoS One"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1385\/MN:26:1:045","article-title":"Neurobiology of glaucomatous optic neuropathy: diverse cellular events in neurodegeneration and neuroprotection","volume":"26","author":"Wax","year":"2002","journal-title":"Mol Neurobiol"},{"key":"bib48","first-page":"82","article-title":"Scleral fibroblast response to experimental glaucoma in mice","volume":"22","author":"Oglesby","year":"2016","journal-title":"Mol Vis"},{"key":"bib49","doi-asserted-by":"publisher","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":"bib50","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/S0021-5155(01)00414-2","article-title":"Distribution and expression of transforming growth factor-beta and platelet-derived growth factor in the normal and glaucomatous monkey optic nerve heads","volume":"45","author":"Fukuchi","year":"2001","journal-title":"Jpn J Ophthalmol"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1167\/iovs.07-1053","article-title":"The effect of TGF-beta2 on elastin, type VI collagen, and components of the proteolytic degradation system in human optic nerve astrocytes","volume":"49","author":"Neumann","year":"2008","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib53","first-page":"1165","article-title":"Systemic Rho kinase inhibition protects optic nerve axons against acute intraocular pressure elevation through stabilization of astrocyte cytoskeleton and connexin43 gap junctions","volume":"61","author":"Tehrani","year":"2020","journal-title":"ARVO Abstract. Invest Ophthalmol Vis Sci."},{"key":"bib54","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1093\/brain\/awm284","article-title":"ROCK inhibition and CNTF interact on intrinsic signaling pathways and differentially regulate survival and regeneration in retinal ganglion cells","volume":"131","author":"Lingor","year":"2008","journal-title":"Brain"},{"issue":"1","key":"bib55","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1167\/iovs.18-25447","article-title":"Optic nerve head astrocytes display axon-dependent and -independent reactivity in response to acutely elevated intraocular pressure","volume":"60","author":"Tehrani","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"4","key":"bib56","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.jphs.2024.02.011","article-title":"Drug combination of topical ripasudil and brimonidine enhances neuroprotection in a mouse model of optic nerve injury","volume":"154","author":"Namekata","year":"2024","journal-title":"J Pharmacol Sci"},{"issue":"7","key":"bib57","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1016\/j.ymthe.2023.03.035","article-title":"Ocular stress enhances contralateral transfer of lenadogene nolparvovec gene therapy through astrocyte networks","volume":"31","author":"McGrady","year":"2023","journal-title":"Mol Ther"},{"key":"bib52","first-page":"13719","article-title":"Regional gene expression in the retina, optic nerve head, and optic nerve of mice with experimental glaucoma and optic nerve crush","volume-title":"Int J Mol Sci","author":"Keuthan","year":"2023"}],"container-title":["Investigative Ophthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2802265","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:55Z","timestamp":1791927115000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2802265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,20]]},"references-count":57,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2024,11,4]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.65.13.43","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2024,11,20]]}}}