{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:52:56Z","timestamp":1768510376752,"version":"3.49.0"},"posted":{"date-parts":[[2024,2,11]]},"group-title":"Molecular Biology","reference-count":66,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,2,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>\n                    The rat Controlled Elevation of Intraocular pressure (CEI) model allows study of\n                    <jats:italic>in vivo<\/jats:italic>\n                    responses to defined intraocular pressures (IOP). In this study, we use Nanostring technology to investigate\n                    <jats:italic>in vivo<\/jats:italic>\n                    IOP-related gene responses in the trabecular meshwork (TM) and optic nerve head (ONH) simultaneously from the same animals.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Male and female rats (N=35) were subject to CEI for 8-hours at pressures simulating mean, daytime normotensive rat IOP (CEI-20), or 2.5x IOP (CEI-50). Na\u00efve animals, receiving no anesthesia or surgical interventions, served as controls. Immediately after CEI, TM and ONH tissues were dissected, RNA isolated, and samples were analyzed with a Nanostring panel containing 770 genes. Post-processing, raw count data were uploaded to Rosalind\u00ae for differential gene expression analyses.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>For the TM, 45 IOP-related genes were significant in the \u201cCEI-50 vs. CEI-20\u201d and \u201cCEI-50 vs. na\u00efve\u201d comparisons, with 15 genes common to both comparisons. Bioinformatics analysis identified Notch and TGF\u03b2 pathways to be the most up- and down-regulated KEGG pathways, respectively. For ONH, 22 significantly regulated genes were identified in the \u201cCEI-50 vs. na\u00efve\u201d comparison. Pathway analysis identified \u2018defense response\u2019 and \u2018immune response\u2019 as two significantly upregulated biological process pathways.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study demonstrates the ability to assay IOP-responsive genes in both TM and ONH tissues simultaneously. In the TM, downregulation of TGF\u03b2 pathway genes suggest that TM responses may prevent TGF\u03b2-induced extracellular matrix synthesis. For ONH, the initial response to elevated IOP may be protective, with astrocytes playing a key role in these gene responses.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.02.11.579818","type":"posted-content","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T07:35:20Z","timestamp":1707723320000},"source":"Crossref","is-referenced-by-count":1,"title":["Profiling IOP-responsive genes in anterior and posterior ocular tissues in the rat CEI glaucoma model"],"prefix":"10.64898","author":[{"given":"Diana C.","family":"Lozano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Feng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William O.","family":"Cepurna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara F.","family":"Smoody","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliesa","family":"Ing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John C.","family":"Morrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1616-972X","authenticated-orcid":false,"given":"Kate E.","family":"Keller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024021320150725000_2024.02.11.579818v1.1","doi-asserted-by":"crossref","first-page":"100897","DOI":"10.1016\/j.preteyeres.2020.100897","article-title":"Normal and glaucomatous outflow regulation","volume":"82","year":"2021","journal-title":"Prog Retin Eye Res"},{"key":"2024021320150725000_2024.02.11.579818v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20030"},{"key":"2024021320150725000_2024.02.11.579818v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(03)00018-1"},{"key":"2024021320150725000_2024.02.11.579818v1.4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.051508.135728"},{"key":"2024021320150725000_2024.02.11.579818v1.5","first-page":"635","article-title":"Optic nerve damage in human glaucoma","volume":"99","year":"1981","journal-title":"II. The site of injury and susceptibility to damage. Arch Ophthalmol"},{"key":"2024021320150725000_2024.02.11.579818v1.6","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0075"},{"key":"2024021320150725000_2024.02.11.579818v1.7","first-page":"534","article-title":"Alterations in gene expression induced by cyclic mechanical stress in trabecular meshwork cells","volume":"15","year":"2009","journal-title":"Mol Vis"},{"key":"2024021320150725000_2024.02.11.579818v1.8","first-page":"1505","article-title":"Effects of mechanical stretching on trabecular matrix metalloproteinases","volume":"42","year":"2001","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2024021320150725000_2024.02.11.579818v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(91)90024-9"},{"key":"2024021320150725000_2024.02.11.579818v1.10","doi-asserted-by":"publisher","DOI":"10.1097\/01.ijg.0000169397.32674.5e"},{"key":"2024021320150725000_2024.02.11.579818v1.11","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-8133"},{"key":"2024021320150725000_2024.02.11.579818v1.12","first-page":"352","article-title":"Genes upregulated in the human trabecular meshwork in response to elevated intraocular pressure","volume":"41","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2024021320150725000_2024.02.11.579818v1.13","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.exer.2016.06.009","article-title":"Pressure-induced expression changes in segmental flow regions of the human trabecular meshwork","volume":"158","year":"2017","journal-title":"Exp Eye Res"},{"key":"2024021320150725000_2024.02.11.579818v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/7741"},{"key":"2024021320150725000_2024.02.11.579818v1.15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58183"},{"key":"2024021320150725000_2024.02.11.579818v1.16","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4567"},{"key":"2024021320150725000_2024.02.11.579818v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2013.10.017"},{"key":"2024021320150725000_2024.02.11.579818v1.18","doi-asserted-by":"crossref","first-page":"5485","DOI":"10.1167\/iovs.15-16993","article-title":"Gremlin Induces Ocular Hypertension in Mice Through Smad3-Dependent Signaling","volume":"56","year":"2015","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2024021320150725000_2024.02.11.579818v1.19","first-page":"1056","article-title":"Increased expression of the WNT antagonist sFRP-1 in glaucoma elevates intraocular pressure","volume":"118","year":"2008","journal-title":"J Clin Invest"},{"key":"2024021320150725000_2024.02.11.579818v1.20","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9664"},{"key":"2024021320150725000_2024.02.11.579818v1.21","first-page":"2151","article-title":"sCD44 overexpression increases intraocular pressure and aqueous outflow resistance","volume":"19","year":"2013","journal-title":"Mol Vis"},{"key":"2024021320150725000_2024.02.11.579818v1.22","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-3947"},{"key":"2024021320150725000_2024.02.11.579818v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.05.012"},{"key":"2024021320150725000_2024.02.11.579818v1.24","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1996.0184"},{"key":"2024021320150725000_2024.02.11.579818v1.25","first-page":"402","article-title":"Translimbal laser photocoagulation to the trabecular meshwork as a model of glaucoma in rats","volume":"43","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2024021320150725000_2024.02.11.579818v1.26","doi-asserted-by":"crossref","first-page":"6700","DOI":"10.1167\/iovs.16-20573","article-title":"A Period of Controlled Elevation of IOP (CEI) Produces the Specific Gene Expression Responses and Focal Injury Pattern of Experimental Rat Glaucoma","volume":"57","year":"2016","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2024021320150725000_2024.02.11.579818v1.27","doi-asserted-by":"crossref","unstructured":"Lozano DC , Jayaram H , Cepurna WO , et al. Optic Nerve Head Gene Transcription Sequelae to a Single Elevated IOP Exposure Provides Insights Into Known Responses to Chronically Elevated IOP. Invest Ophthalmol Vis Sci 2023;64:4.","DOI":"10.1167\/iovs.64.10.4"},{"key":"2024021320150725000_2024.02.11.579818v1.28","doi-asserted-by":"crossref","first-page":"109367","DOI":"10.1016\/j.exer.2022.109367","article-title":"A method describing the microdissection of trabecular meshwork tissue from Brown Norway rat eyes","volume":"228","year":"2023","journal-title":"Exp Eye Res"},{"key":"2024021320150725000_2024.02.11.579818v1.29","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3109\/07420528.2015.1008135","article-title":"Circadian rhythm of intraocular pressure in the adult rat","volume":"32","year":"2015","journal-title":"Chronobiol Int"},{"key":"2024021320150725000_2024.02.11.579818v1.30","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3109\/02713689608997412","article-title":"Circadian rhythm of intraocular pressure in the rat","volume":"15","year":"1996","journal-title":"Curr Eye Res"},{"key":"2024021320150725000_2024.02.11.579818v1.31","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-3921"},{"key":"2024021320150725000_2024.02.11.579818v1.32","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.exer.2013.04.008","article-title":"The dark phase intraocular pressure elevation and retinal ganglion cell degeneration in a rat model of experimental glaucoma","volume":"112","year":"2013","journal-title":"Exp Eye Res"},{"key":"2024021320150725000_2024.02.11.579818v1.33","doi-asserted-by":"crossref","first-page":"e0280332","DOI":"10.1371\/journal.pone.0280332","article-title":"A portable feedback-controlled pump for monitoring eye outflow facility in conscious rats","volume":"18","year":"2023","journal-title":"PLoS One"},{"key":"2024021320150725000_2024.02.11.579818v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2004.08.003"},{"key":"2024021320150725000_2024.02.11.579818v1.35","doi-asserted-by":"crossref","first-page":"100799","DOI":"10.1016\/j.preteyeres.2019.100799","article-title":"Inducible rodent models of glaucoma","volume":"75","year":"2020","journal-title":"Prog Retin Eye Res"},{"key":"2024021320150725000_2024.02.11.579818v1.36","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.90261.2008"},{"key":"2024021320150725000_2024.02.11.579818v1.37","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5317"},{"key":"2024021320150725000_2024.02.11.579818v1.38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.108175"},{"key":"2024021320150725000_2024.02.11.579818v1.39","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1172\/JCI120879","article-title":"Angiopoietin-like 4 binds neuropilins and cooperates with VEGF to induce diabetic macular edema","volume":"129","year":"2019","journal-title":"J Clin Invest"},{"key":"2024021320150725000_2024.02.11.579818v1.40","doi-asserted-by":"crossref","first-page":"108935","DOI":"10.1016\/j.exer.2022.108935","article-title":"Endogenous expression of Notch pathway molecules in human trabecular meshwork cells","volume":"216","year":"2022","journal-title":"Exp Eye Res"},{"key":"2024021320150725000_2024.02.11.579818v1.41","doi-asserted-by":"crossref","unstructured":"Stassen O , Ristori T , Sahlgren CM . Notch in mechanotransduction - from molecular mechanosensitivity to tissue mechanostasis. J Cell Sci 2020;133.","DOI":"10.1242\/jcs.250738"},{"key":"2024021320150725000_2024.02.11.579818v1.42","first-page":"237","article-title":"Genomic\/proteomic analyses of dexamethasone-treated human trabecular meshwork cells reveal a role for GULP1 and ABR in phagocytosis","volume":"25","year":"2019","journal-title":"Mol Vis"},{"key":"2024021320150725000_2024.02.11.579818v1.43","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.jprot.2011.02.024","article-title":"Protein profile of exosomes from trabecular meshwork cells","volume":"74","year":"2011","journal-title":"Journal of proteomics"},{"key":"2024021320150725000_2024.02.11.579818v1.44","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-12652"},{"key":"2024021320150725000_2024.02.11.579818v1.45","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1167\/iovs.17-21964","article-title":"The Role of Wnt\/beta-Catenin Signaling and K-Cadherin in the Regulation of Intraocular Pressure","volume":"59","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2024021320150725000_2024.02.11.579818v1.46","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.449983"},{"key":"2024021320150725000_2024.02.11.579818v1.47","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","year":"2017","journal-title":"Exp Eye Res"},{"key":"2024021320150725000_2024.02.11.579818v1.48","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1994.1158"},{"key":"2024021320150725000_2024.02.11.579818v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(98)00011-1"},{"key":"2024021320150725000_2024.02.11.579818v1.50","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3434"},{"key":"2024021320150725000_2024.02.11.579818v1.51","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.exer.2016.08.023","article-title":"Role of the Rho GTPase\/Rho kinase signaling pathway in pathogenesis and treatment of glaucoma: Bench to bedside research","volume":"158","year":"2017","journal-title":"Exp Eye Res"},{"key":"2024021320150725000_2024.02.11.579818v1.52","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1167\/iovs.16-20779","article-title":"VEGF as a Paracrine Regulator of Conventional Outflow Facility","volume":"58","year":"2017","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2024021320150725000_2024.02.11.579818v1.53","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1167\/iovs.18-25700","article-title":"Early Optic Nerve Head Glial Proliferation and Jak-Stat Pathway Activation in Chronic Experimental Glaucoma","volume":"60","year":"2019","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2024021320150725000_2024.02.11.579818v1.54","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-1282"},{"key":"2024021320150725000_2024.02.11.579818v1.55","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy274"},{"key":"2024021320150725000_2024.02.11.579818v1.56","doi-asserted-by":"crossref","first-page":"950","DOI":"10.3389\/fimmu.2019.00950","article-title":"Reduced Angiopoietin-Like 4 Expression in Multiple Sclerosis Lesions Facilitates Lipid Uptake by Phagocytes via Modulation of Lipoprotein-Lipase Activity","volume":"10","year":"2019","journal-title":"Front Immunol"},{"key":"2024021320150725000_2024.02.11.579818v1.57","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(20000101)29:1<91::AID-GLIA9>3.0.CO;2-I"},{"key":"2024021320150725000_2024.02.11.579818v1.58","doi-asserted-by":"crossref","first-page":"14474","DOI":"10.1038\/s41598-020-71329-8","article-title":"Metabolic alterations in Parkinson\u2019s disease astrocytes","volume":"10","year":"2020","journal-title":"Sci Rep"},{"key":"2024021320150725000_2024.02.11.579818v1.59","doi-asserted-by":"publisher","DOI":"10.1002\/glia.440140107"},{"key":"2024021320150725000_2024.02.11.579818v1.60","first-page":"2704","article-title":"Human optic nerve head astrocytes as a target for endothelin-1","volume":"43","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2024021320150725000_2024.02.11.579818v1.61","first-page":"135","article-title":"An endothelin-1-induced model of chronic optic nerve ischemia in rhesus monkeys","volume":"5","year":"1996","journal-title":"J Glaucoma"},{"key":"2024021320150725000_2024.02.11.579818v1.62","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-0687"},{"key":"2024021320150725000_2024.02.11.579818v1.63","unstructured":"The R Project for Statistical Computing."},{"key":"2024021320150725000_2024.02.11.579818v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.01.045"},{"key":"2024021320150725000_2024.02.11.579818v1.65","doi-asserted-by":"crossref","unstructured":"Sakamoto N , Okuno D , Tokito T , et al. HSP47: A Therapeutic Target in Pulmonary Fibrosis. Biomedicines 2023;11.","DOI":"10.3390\/biomedicines11092387"},{"key":"2024021320150725000_2024.02.11.579818v1.66","first-page":"2649","article-title":"Effect of matrix metalloproteinases activity on outflow in perfused human organ culture","volume":"39","year":"1998","journal-title":"Invest Ophthalmol Vis Sci"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.02.11.579818","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:55:50Z","timestamp":1768456550000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.02.11.579818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,11]]},"references-count":66,"URL":"https:\/\/doi.org\/10.1101\/2024.02.11.579818","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1167\/iovs.65.5.41","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2024,2,11]]},"subtype":"preprint"}}