{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:59:39Z","timestamp":1791928779118,"version":"4.3.4"},"reference-count":40,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"8","license":[{"start":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000},"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":[[2022,7,8]]},"DOI":"10.1167\/iovs.63.8.2","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T11:33:06Z","timestamp":1657279986000},"page":"2","source":"Crossref","is-referenced-by-count":60,"title":["Hypoxia-Induced Scleral HIF-2\u03b1 Upregulation Contributes to Rises in MMP-2 Expression and Myopia Development in Mice"],"prefix":"10.1167","volume":"63","author":[{"given":"Wenjing","family":"Wu","sequence":"first","affiliation":[{"name":"School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchao","family":"Su","sequence":"additional","affiliation":[{"name":"School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxi","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixin","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guandong","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiadi","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhai","sequence":"additional","affiliation":[{"name":"School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Qu","sequence":"additional","affiliation":[{"name":"School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China"},{"name":"National Clinical Research Center for Ocular Diseases, Wenzhou, Zhejiang, China"},{"name":"Oujiang Laboratory, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangtian","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China"},{"name":"National Clinical Research Center for Ocular Diseases, Wenzhou, Zhejiang, China"},{"name":"Research Unit of Myopia Basic Research and Clinical Prevention and Control, Chinese Academy of Medical Sciences (2019RU025), Wenzhou, Zhejiang, China"},{"name":"Oujiang Laboratory, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"State Key Laboratory of Optometry, Ophthalmology, and Vision Science, Wenzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1016\/S0140-6736(12)60272-4","article-title":"Myopia","volume":"379","author":"Morgan","year":"2012","journal-title":"Lancet (London, England)"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1167\/iovs.62.5.3","article-title":"IMI Risk Factors for Myopia","volume":"62","author":"Morgan","year":"2021","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1016\/j.ophtha.2016.01.006","article-title":"Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050","volume":"123","author":"Holden","year":"2016","journal-title":"Ophthalmology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1097\/IAE.0000000000001489","article-title":"Overview of the complications of high myopia","volume":"37","author":"Ikuno","year":"2017","journal-title":"Retina (Philadelphia, Pa)"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.exer.2013.01.014","article-title":"Regulation of scleral metabolism in myopia and the role of transforming growth factor-beta","volume":"114","author":"McBrien","year":"2013","journal-title":"Exp Eye Res"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.neuron.2004.08.008","article-title":"Homeostasis of eye growth and the question of myopia","volume":"43","author":"Wallman","year":"2004","journal-title":"Neuron"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1006\/exer.1996.0127","article-title":"Scleral matrix metalloproteinases, serine proteinase activity and hydrational capacity are increased in myopia induced by retinal image degradation","volume":"63","author":"Jones","year":"1996","journal-title":"Exp Eye Res"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.exer.2005.08.009","article-title":"The sclera and myopia","volume":"82","author":"Rada","year":"2006","journal-title":"Exp Eye Res"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1016\/j.ajpath.2018.04.011","article-title":"Cause and Effect Relationship between Changes in Scleral Matrix Metallopeptidase-2 Expression and Myopia Development in Mice","volume":"188","author":"Zhao","year":"2018","journal-title":"Am J Pathol"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.ajpath.2020.06.002","article-title":"Up-Regulation of Matrix Metalloproteinase-2 by Scleral Monocyte-Derived Macrophages Contributes to Myopia Development","volume":"190","author":"Zhao","year":"2020","journal-title":"Am J Pathol"},{"key":"bib11","doi-asserted-by":"crossref","first-page":"E7091","DOI":"10.1073\/pnas.1721443115","article-title":"Scleral hypoxia is a target for myopia control","volume":"115","author":"Wu","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"102878","DOI":"10.1016\/j.ebiom.2020.102878","article-title":"Scleral HIF-1a is a prominent regulatory candidate for genetic and environmental interactions in human myopia pathogenesis","volume":"57","author":"Zhao","year":"2020","journal-title":"EBioMedicine"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1161\/01.RES.0000015588.70132.DC","article-title":"Regulation of endothelial matrix metalloproteinase-2 by hypoxia\/reoxygenation","volume":"90","author":"Ben-Yosef","year":"2002","journal-title":"Circulation Res"},{"key":"bib14","first-page":"399","article-title":"HIF-1a contributes to hypoxia-induced invasion and metastasis of esophageal carcinoma via inhibiting E-cadherin and promoting MMP-2 expression","volume":"66","author":"Jing","year":"2012","journal-title":"Acta Medica Okayama"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.yjmcc.2018.06.006","article-title":"MMP-2 and MMP-9 contribute to the angiogenic effect produced by hypoxia\/15-HETE in pulmonary endothelial cells","volume":"121","author":"Liu","year":"2018","journal-title":"J Molec Cell Cardiol"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"2379","DOI":"10.1038\/sj.onc.1209273","article-title":"Hypoxia stimulates breast carcinoma cell invasion through MT1-MMP and MMP-2 activation","volume":"25","author":"Mu\u00f1oz-N\u00e1jar","year":"2006","journal-title":"Oncogene"},{"key":"bib17","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1007\/BF02828202","article-title":"Hypoxia down-regulates secretion of MMP-2, MMP-9 in porcine pulmonary artery endothelial and smooth muscle cells and the role of HIF-1","volume":"25","author":"Ye","year":"2005","journal-title":"J Huazhong Univ Sci Technol Med Sci"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.yjmcc.2009.06.002","article-title":"Chronic hypoxia inhibits MMP-2 activation and cellular invasion in human cardiac myofibroblasts","volume":"47","author":"Riches","year":"2009","journal-title":"J Molec Cell Cardiol"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"3743","DOI":"10.3892\/ol.2016.4471","article-title":"Knockdown of hypoxia inducible factor-2a inhibits cell invasion via the downregulation of MMP-2 expression in breast cancer cells","volume":"11","author":"Li","year":"2016","journal-title":"Oncol Lett"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.jcmgh.2015.09.005","article-title":"Role of Hypoxia-Inducible Factors in the Development of Liver Fibrosis","volume":"1","author":"Roth","year":"2015","journal-title":"Cell Molec Gastroenterol Hepatol"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.cell.2012.01.021","article-title":"Hypoxia-inducible factors in physiology and medicine","volume":"148","author":"Semenza","year":"2012","journal-title":"Cell"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1111\/opo.v40.5","article-title":"Topical bendazol inhibits experimental myopia progression and decreases the ocular accumulation of HIF-1a protein in young rabbits","volume":"40","author":"Tong","year":"2020","journal-title":"Ophthalmic Physiological Optics"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1097\/00006324-200402000-00008","article-title":"Measurement of refractive state and deprivation myopia in two strains of mice","volume":"81","author":"Schaeffel","year":"2004","journal-title":"Optom Vis Sci"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"5208","DOI":"10.1167\/iovs.07-1545","article-title":"The development of the refractive status and ocular growth in C57BL\/6 mice","volume":"49","author":"Zhou","year":"2008","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1080\/02713680600770609","article-title":"The presence of m1 to m5 receptors in human sclera: evidence of the sclera as a potential site of action for muscarinic receptor antagonists","volume":"31","author":"Qu","year":"2006","journal-title":"Current Eye Res"},{"key":"bib26","doi-asserted-by":"publisher","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(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods (San Diego, Calif)"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/s41586-019-0874-3","article-title":"HIF-1a metabolically controls collagen synthesis and modification in chondrocytes","volume":"565","author":"Stegen","year":"2019","journal-title":"Nature"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"4473","DOI":"10.1242\/dev.083881","article-title":"HIF1a is a central regulator of collagen hydroxylation and secretion under hypoxia during bone development","volume":"139","author":"Bentovim","year":"2012","journal-title":"Development (Cambridge, England)"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s00441-009-0841-7","article-title":"Extracellular matrix genes as hypoxia-inducible targets","volume":"339","author":"Myllyharju","year":"2010","journal-title":"Cell Tissue Res"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1002\/iub.v68.9","article-title":"Hypoxia inducible factor 1 alpha down-regulates type i collagen through Sp3 transcription factor in human chondrocytes","volume":"68","author":"Duval","year":"2016","journal-title":"IUBMB Life"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"3038","DOI":"10.1002\/art.v60:10","article-title":"Hypoxia-inducible factor 1alpha inhibits the fibroblast-like markers type I and type III collagen during hypoxia-induced chondrocyte redifferentiation: hypoxia not only induces type II collagen and aggrecan, but it also inhibits type I and type III collagen in the hypoxia-inducible factor 1alpha-dependent redifferentiation of chondrocytes","volume":"60","author":"Duval","year":"2009","journal-title":"Arthritis Rheumatism"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1096\/fsb2.v15.13","article-title":"HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia","volume":"15","author":"Stroka","year":"2001","journal-title":"FASEB J"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1096\/fsb2.v17.2","article-title":"Widespread hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organs","volume":"17","author":"Wiesener","year":"2003","journal-title":"FASEB J"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/j.celrep.2014.02.011","article-title":"Hypoxia-inducible factor 3 is an oxygen-dependent transcription activator and regulates a distinct transcriptional response to hypoxia","volume":"6","author":"Zhang","year":"2014","journal-title":"Cell Rep"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"C260","DOI":"10.1152\/ajpcell.00315.2015","article-title":"Hypoxia-inducible factor 3 biology: complexities and emerging themes","volume":"310","author":"Duan","year":"2016","journal-title":"Am J Physiol Cell Physiol"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"109018","DOI":"10.1016\/j.exer.2022.109018","article-title":"Form-deprivation myopia downregulates calcium levels in retinal horizontal cells in mice","volume":"218","author":"Li","year":"2022","journal-title":"Exp Eye Res"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1136\/jmedgenet-2020-107220","article-title":"Dysfunction of VIPR2 leads to myopia in humans and mice","volume":"59","author":"Zhao","year":"2022","journal-title":"J Med Genetics"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"107956","DOI":"10.1016\/j.exer.2020.107956","article-title":"Increased endogenous dopamine prevents myopia in mice","volume":"193","author":"Landis","year":"2020","journal-title":"Exp Eye Res"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"4412","DOI":"10.1167\/iovs.15-17784","article-title":"Altered Refractive Development in Mice With Reduced Levels of Retinal Dopamine","volume":"57","author":"Bergen","year":"2016","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1111\/cxo.12312","article-title":"Animal models in myopia research","volume":"98","author":"Schaeffel","year":"2015","journal-title":"Clin Exp Optom"}],"container-title":["Investigative Opthalmology & Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2783450","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:33Z","timestamp":1791927093000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2783450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,8]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,7,8]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.63.8.2","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2022,7,8]]}}}