{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:35:53Z","timestamp":1787826953154,"version":"build-2784847793"},"reference-count":42,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T00:00:00Z","timestamp":1571270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T00:00:00Z","timestamp":1571270400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T00:00:00Z","timestamp":1571270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL124120"],"award-info":[{"award-number":["R01 HL124120"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 EY025799"],"award-info":[{"award-number":["R01 EY025799"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 DK114857"],"award-info":[{"award-number":["P30 DK114857"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Elevated intraocular pressure (IOP) due to insufficient aqueous humor outflow through the trabecular meshwork and Schlemm\u2019s canal (SC) is the most important risk factor for glaucoma, a leading cause of blindness worldwide. We previously reported loss of function mutations in the receptor tyrosine kinase TEK or its ligand ANGPT1 cause primary congenital glaucoma in humans and mice due to failure of SC development. Here, we describe a novel approach to enhance canal formation in these animals by deleting a single allele of the gene encoding the phosphatase PTPRB during development. Compared to\n                    <jats:italic>Tek<\/jats:italic>\n                    haploinsufficient mice, which exhibit elevated IOP and loss of retinal ganglion cells,\n                    <jats:italic>Tek<\/jats:italic>\n                    <jats:sup>+\/-<\/jats:sup>\n                    ;\n                    <jats:italic>Ptprb<\/jats:italic>\n                    <jats:sup>+\/-<\/jats:sup>\n                    mice have elevated TEK phosphorylation, which allows normal SC development and prevents ocular hypertension and RGC loss. These studies provide evidence that PTPRB is an important regulator of TEK signaling in the aqueous humor outflow pathway and identify a new therapeutic target for treatment of glaucoma.\n                  <\/jats:p>","DOI":"10.7554\/elife.48474","type":"journal-article","created":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T08:00:29Z","timestamp":1571299229000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.48474","source":"Crossref","is-referenced-by-count":37,"title":["Targeting the vascular-specific phosphatase PTPRB protects against retinal ganglion cell loss in a pre-clinical model of glaucoma"],"prefix":"10.7554","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6565-5866","authenticated-orcid":true,"given":"Benjamin R","family":"Thomson","sequence":"first","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, United States"},{"name":"Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7980-2377","authenticated-orcid":true,"given":"Isabel A","family":"Carota","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, United States"},{"name":"Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3285-8613","authenticated-orcid":true,"given":"Tomokazu","family":"Souma","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, United States"},{"name":"Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saily","family":"Soman","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, United States"},{"name":"Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3517-732X","authenticated-orcid":true,"given":"Dietmar","family":"Vestweber","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Molecular Biomedicine, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3706-5727","authenticated-orcid":true,"given":"Susan E","family":"Quaggin","sequence":"additional","affiliation":[{"name":"Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, United States"},{"name":"Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2019,10,17]]},"reference":[{"key":"bib1","article-title":"Aerpio pharmaceuticals announces results from time-2b study of akb-9778 in diabetic retinopathy [Press release]","author":"Aerpio Pharmaceuticals Inc","year":"2019","unstructured":"Aerpio Pharmaceuticals Inc. 2019. Aerpio pharmaceuticals announces results from time-2b study of akb-9778 in diabetic retinopathy [Press release]. http:\/\/ir.aerpio.com\/phoenix.zhtml?c=254540&p=irol-newsArticle&ID=2391547 [Accessed March 18, 2019]."},{"key":"bib2","doi-asserted-by":"publisher","first-page":"3975","DOI":"10.1172\/JCI75395","article-title":"The schlemm's canal is a VEGF-C\/VEGFR-3-responsive lymphatic-like vessel","volume":"124","author":"Aspelund","year":"2014","journal-title":"Journal of Clinical Investigation"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"4754","DOI":"10.1182\/blood-2006-01-0141","article-title":"Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development","volume":"107","author":"B\u00e4umer","year":"2006","journal-title":"Blood"},{"key":"bib4","first-page":"156","article-title":"Tonography in the diagnosis of simple (open angle) glaucoma","volume":"65","author":"Becker","year":"1961","journal-title":"Transactions - American Academy of Ophthalmology and Otolaryngology"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gni051","article-title":"Conditional and inducible transgene expression in mice through the combinatorial use of Cre-mediated recombination and tetracycline induction","volume":"33","author":"Belteki","year":"2005","journal-title":"Nucleic Acids Research"},{"key":"bib6","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201847046","article-title":"VE-PTP inhibition stabilizes endothelial junctions by activating FGD5","volume":"20","author":"Braun","year":"2019","journal-title":"EMBO Reports"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1084\/jem.20110525","article-title":"Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo","volume":"208","author":"Broermann","year":"2011","journal-title":"The Journal of Experimental Medicine"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"1722","DOI":"10.1016\/j.ophtha.2016.04.025","article-title":"Enhanced benefit in diabetic macular edema from AKB-9778 Tie2 activation combined with vascular endothelial growth factor suppression","volume":"123","author":"Campochiaro","year":"2016","journal-title":"Ophthalmology"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1084\/jem.20180009","article-title":"Targeting VE-PTP phosphatase protects the kidney from diabetic injury","volume":"216","author":"Carota","year":"2019","journal-title":"The Journal of Experimental Medicine"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1016\/j.survophthal.2008.08.006","article-title":"Risk factors for Glaucoma onset and progression","volume":"53 Suppl1","author":"Coleman","year":"2008","journal-title":"Survey of Ophthalmology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"E3179","DOI":"10.1073\/pnas.1217812110","article-title":"Conditionals by inversion provide a universal method for the generation of conditional alleles","volume":"110","author":"Economides","year":"2013","journal-title":"PNAS"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"5948","DOI":"10.1038\/sj.onc.1202992","article-title":"Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the angiopoietin receptor Tie-2","volume":"18","author":"Fachinger","year":"1999","journal-title":"Oncogene"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1093\/hmg\/ddy111","article-title":"Genome-wide association analyses identify new loci influencing intraocular pressure","volume":"27","author":"Gao","year":"2018","journal-title":"Human Molecular Genetics"},{"key":"bib14","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2683","article-title":"VE-PTP regulates VEGFR2 activity in stalk cells to establish endothelial cell polarity and lumen formation","volume":"4","author":"Hayashi","year":"2013","journal-title":"Nature Communications"},{"key":"bib15","first-page":"249","article-title":"Intraocular pressure in inbred mouse strains","volume":"38","author":"John","year":"1997","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.exer.2016.01.017","article-title":"Unconventional aqueous humor outflow: a review","volume":"158","author":"Johnson","year":"2017","journal-title":"Experimental Eye Research"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1007\/s00439-017-1823-6","article-title":"Angiopoietin receptor TEK interacts with CYP1B1 in primary congenital Glaucoma","volume":"136","author":"Kabra","year":"2017","journal-title":"Human Genetics"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/s41588-018-0126-8","article-title":"Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle Glaucoma","volume":"50","author":"Khawaja","year":"2018","journal-title":"Nature Genetics"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"20126","DOI":"10.1074\/jbc.M500292200","article-title":"Oligomerization and multimerization are critical for angiopoietin-1 to bind and phosphorylate Tie2","volume":"280","author":"Kim","year":"2005","journal-title":"Journal of Biological Chemistry"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"3877","DOI":"10.1172\/JCI94668","article-title":"Impaired angiopoietin\/Tie2 signaling compromises schlemm's canal integrity and induces glaucoma","volume":"127","author":"Kim","year":"2017","journal-title":"Journal of Clinical Investigation"},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001912","article-title":"Schlemm's canal is a unique vessel with a combination of blood vascular and lymphatic phenotypes that forms by a novel developmental process","volume":"12","author":"Kizhatil","year":"2014","journal-title":"PLOS Biology"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1038\/s41588-018-0176-y","article-title":"Genome-wide association study of intraocular pressure uncovers new pathways to Glaucoma","volume":"50","author":"MacGregor","year":"2018","journal-title":"Nature Genetics"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1096\/fj.08-123810","article-title":"Transcriptional profiling reveals a critical role for tyrosine phosphatase VE-PTP in regulation of VEGFR2 activity and endothelial cell morphogenesis","volume":"23","author":"Mellberg","year":"2009","journal-title":"The FASEB Journal"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1167\/iovs.10-6069","article-title":"Assessment of aqueous humor dynamics in the mouse by a novel method of Constant-Flow infusion","volume":"52","author":"Millar","year":"2011","journal-title":"Investigative Opthalmology & Visual Science"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"5764","DOI":"10.1167\/iovs.15-16720","article-title":"Strain and age effects on aqueous humor dynamics in the mouse","volume":"56","author":"Millar","year":"2015","journal-title":"Investigative Opthalmology & Visual Science"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"4885","DOI":"10.1093\/emboj\/cdf497","article-title":"VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts","volume":"21","author":"Nawroth","year":"2002","journal-title":"The EMBO Journal"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"3960","DOI":"10.1172\/JCI75392","article-title":"Lymphatic regulator PROX1 determines schlemm's canal integrity and identity","volume":"124","author":"Park","year":"2014","journal-title":"Journal of Clinical Investigation"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/j.ccell.2016.10.018","article-title":"Normalization of tumor vessels by Tie2 activation and Ang2 inhibition enhances drug delivery and produces a favorable tumor microenvironment","volume":"30","author":"Park","year":"2016","journal-title":"Cancer Cell"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nrd4051","article-title":"Validating therapeutic targets through human genetics","volume":"12","author":"Plenge","year":"2013","journal-title":"Nature Reviews Drug Discovery"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/nrd.2016.278","article-title":"Therapeutic targeting of the angiopoietin-TIE pathway","volume":"16","author":"Saharinen","year":"2017","journal-title":"Nature Reviews Drug Discovery"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nature Methods"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"4564","DOI":"10.1172\/JCI74527","article-title":"Targeting VE-PTP activates TIE2 and stabilizes the ocular vasculature","volume":"124","author":"Shen","year":"2014","journal-title":"Journal of Clinical Investigation"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"2575","DOI":"10.1172\/JCI85830","article-title":"Angiopoietin receptor TEK mutations underlie primary congenital Glaucoma with variable expressivity","volume":"126","author":"Souma","year":"2016","journal-title":"Journal of Clinical Investigation"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1073\/pnas.1714446115","article-title":"Context-dependent functions of angiopoietin 2 are determined by the endothelial phosphatase VEPTP","volume":"115","author":"Souma","year":"2018","journal-title":"PNAS"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1016\/j.ophtha.2018.04.040","article-title":"Rho kinase inhibitors as a novel treatment for Glaucoma and ocular hypertension","volume":"125","author":"Tanna","year":"2018","journal-title":"Ophthalmology"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"4320","DOI":"10.1172\/JCI77162","article-title":"A lymphatic defect causes ocular hypertension and Glaucoma in mice","volume":"124","author":"Thomson","year":"2014","journal-title":"Journal of Clinical Investigation"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"4421","DOI":"10.1172\/JCI95545","article-title":"Angiopoietin-1 is required for Schlemm's canal development in mice and humans","volume":"127","author":"Thomson","year":"2017","journal-title":"Journal of Clinical Investigation"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/978-1-4939-8712-2_10","volume-title":"Lymphangiogenesis: Methods and Protocols","author":"Thomson","year":"2018"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/S0002-9394(98)00436-X","article-title":"Aqueous humor dynamics in the aging human eye","volume":"127","author":"Toris","year":"1999","journal-title":"American Journal of Ophthalmology"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1089\/jop.2000.16.19","article-title":"Aqueous humor dynamics in monkeys with laser-induced Glaucoma","volume":"16","author":"Toris","year":"2000","journal-title":"Journal of Ocular Pharmacology and Therapeutics"},{"key":"bib41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098245","article-title":"Novel characterization and live imaging of schlemm's canal expressing Prox-1","volume":"9","author":"Truong","year":"2014","journal-title":"PLOS ONE"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1083\/jcb.200811159","article-title":"VE-PTP controls blood vessel development by balancing Tie-2 activity","volume":"185","author":"Winderlich","year":"2009","journal-title":"The Journal of Cell Biology"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/48474\/elife-48474-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/48474\/elife-48474-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/48474","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:01:25Z","timestamp":1697058085000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/48474"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,17]]},"references-count":42,"alternative-id":["10.7554\/eLife.48474"],"URL":"https:\/\/doi.org\/10.7554\/elife.48474","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.48474.sa1","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.48474.sa2","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,17]]},"article-number":"e48474"}}