ArticleThe Journal of clinical investigation2017
Impaired angiopoietin/Tie2 signaling compromises Schlemm's canal integrity and induces glaucoma.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.
- Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma.Nature communications · 2025Pooled it
- Tie2 Activation via VE-PTP Inhibition With Razuprotafib as an Adjunct to Latanoprost in Patients With Open Angle Glaucoma or Ocular Hypertension.Translational vision science & technology · 2022Trial
- A Small Molecule Inhibitor of VE-PTP Activates Tie2 in Schlemm's Canal Increasing Outflow Facility and Reducing Intraocular Pressure.Investigative ophthalmology & visual science · 2020Trial
- Receptor tyrosine kinase signaling in mammalian eye development.Developmental biology · 2026Review
- VEGFA-Positive Macrophages Regulate Aqueous Humor Outflow in Aged Mice and Humans.bioRxiv : the preprint server for biology · 2026Article
- Schlemm's Canal Development and Implications for Glaucoma Treatment.Annual review of vision science · 2026Review
- Article
- Ocular Lymphatics in Health and Disease.Diagnostics (Basel, Switzerland) · 2026Review
- Uncovering a Glaucoma-Linked Lysophosphatidic Acid-MAPK/AP-1 Fibrosis Axis in Human Trabecular Meshwork Cells and Its Modulation byInternational journal of molecular sciences · 2026Article
- Time-Dependent Glucocorticoid-Induced Transcriptomic Changes in Human Trabecular Meshwork and Schlemm's Canal Cells.Investigative ophthalmology & visual science · 2026Article
- Time-dependent Glucocorticoid-Induced Transcriptomic Changes in Human Trabecular Meshwork and Schlemm's Canal.bioRxiv : the preprint server for biology · 2026Article
- Human ocular fluid outflow on-chip reveals trabecular meshwork-mediated Schlemm's canal endothelial dysfunction in steroid-induced glaucoma.Nature cardiovascular research · 2025Article
- Comparison of intraocular pressure changes in Japanese patients with neovascular age-related macular degeneration treated with aflibercept or faricimab.Japanese journal of ophthalmology · 2025Observational
- Phase Ib Clinical and Pharmacodynamic Study of the TIE2 Kinase Inhibitor Rebastinib with Paclitaxel or Eribulin in HER2-Negative Metastatic Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Article
- Schlemm's canal-selective Tie2/TEK knockdown induces sustained ocular hypertension in adult mice.Experimental eye research · 2024Article
- Article
- Insights to Ang/Tie signaling pathway: another rosy dawn for treating retinal and choroidal vascular diseases.Journal of translational medicine · 2024Review
- Transcriptomic profiling of Schlemm's canal cells reveals a lymphatic-biased identity and three major cell states.bioRxiv : the preprint server for biology · 2024Article
- High throughput functional profiling of genes at intraocular pressure loci reveals distinct networks for glaucoma.Human molecular genetics · 2024Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary open-angle glaucoma (POAG) is often caused by elevated intraocular pressure (IOP), which arises due to increased resistance to aqueous humor outflow (AHO). Aqueous humor flows through Schlemm's canal (SC), a lymphatic-like vessel encircling the cornea, and via intercellular spaces of ciliary muscle cells. However, the mechanisms underlying increased AHO resistance are poorly understood. Here, we demonstrate that signaling between angiopoietin (Angpt) and the Angpt receptor Tie2, which is critical for SC formation, is also indispensable for maintaining SC integrity during adulthood. Deletion of Angpt1/Angpt2 or Tie2 in adult mice severely impaired SC integrity and transcytosis, leading to elevated IOP, retinal neuron damage, and impairment of retinal ganglion cell function, all hallmarks of POAG in humans. We found that SC integrity is maintained by interconnected and coordinated functions of Angpt-Tie2 signaling, AHO, and Prox1 activity. These functions diminish in the SC during aging, leading to impaired integrity and transcytosis. Intriguingly, Tie2 reactivation using a Tie2 agonistic antibody rescued the POAG phenotype in Angpt1/Angpt2-deficient mice and rejuvenated the SC in aged mice. These results indicate that the Angpt-Tie2 system is essential for SC integrity. The impairment of this system underlies POAG-associated pathogenesis, supporting the possibility that Tie2 agonists could be a therapeutic option for glaucoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.