ArticleThe Journal of clinical investigation2014
A lymphatic defect causes ocular hypertension and glaucoma in mice.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
114 citing papers in PubMed, 2 syntheses or guidelines pooled it, 225 citations in OpenAlex.
- Rare genetic variation in PTPRB is associated with central serous chorioretinopathy, varicose veins and glaucoma.Nature communications · 2025Pooled it
- Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma.Nature genetics · 2018Pooled 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
- 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
- A human endothelial and adipose stem cell-based co-culture model for venous malformations.Angiogenesis · 2026Article
- Loss of angiopoietin-2 leads to region-specific brain malformations and blood-brain barrier leakage.JCI insight · 2026Article
- A Highly Active Angiopoietin 1 Mimetic Potentiates Angiogenesis in Mouse Models of Choroidal Neovascularization.Translational vision science & technology · 2026Article
- The Undiagnosed Diseases Network (UDN) Solves Ocular Syndromic Diagnostic Dilemmas.American journal of ophthalmology · 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
- Inhibition of Angiopoietin-2 rescues sporadic brain arteriovenous malformations by reducing pericyte loss.Angiogenesis · 2024Article
- Schlemm's canal-selective Tie2/TEK knockdown induces sustained ocular hypertension in adult mice.Experimental eye research · 2024Article
- Glaucoma-Protective Human Single-Nucleotide Polymorphism in theArteriosclerosis, thrombosis, and vascular biology · 2024Article
- Advances in Neuroprotection in Glaucoma: Pharmacological Strategies and Emerging Technologies.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Loss of TGFβ-Mediated Repression of Angiopoietin-2 in Pericytes Underlies Germinal Matrix Hemorrhage Pathogenesis.Stroke · 2024Article
- Consistent Intraocular Pressure Reduction by Solid Drug Nanoparticles in Fixed Combinations for Glaucoma Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Increasing the diagnostic yield of childhood glaucoma cases recruited into the 100,000 Genomes Project.BMC genomics · 2024Article
54 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
17 authors at 6 institutions in 3 countries.
Funding
Abstract
Glaucoma is a leading cause of blindness, afflicting more than 60 million people worldwide. Increased intraocular pressure (IOP) due to impaired aqueous humor drainage is a major risk factor for the development of glaucoma. Here, we demonstrated that genetic disruption of the angiopoietin/TIE2 (ANGPT/TIE2) signaling pathway results in high IOP, buphthalmos, and classic features of glaucoma, including retinal ganglion degeneration and vision loss. Eyes from mice with induced deletion of Angpt1 and Angpt2 (A1A2Flox(WB) mice) lacked drainage pathways in the corneal limbus, including Schlemm's canal and lymphatic capillaries, which share expression of the PROX1, VEGFR3, and FOXC family of transcription factors. VEGFR3 and FOXCs have been linked to lymphatic disorders in patients, and FOXC1 has been linked to glaucoma. In contrast to blood endothelium, in which ANGPT2 is an antagonist of ANGPT1, we have shown that both ligands cooperate to regulate TIE2 in the lymphatic network of the eye. While A1A2Flox(WB) mice developed high IOP and glaucoma, expression of ANGPT1 or ANGPT2 alone was sufficient for ocular drainage. Furthermore, we demonstrated that loss of FOXC2 from lymphatics results in TIE2 downregulation, suggesting a mechanism for ocular defects in patients with FOXC mutations. These data reveal a pathogenetic and molecular basis for glaucoma and demonstrate the importance of angiopoietin ligand cooperation in the lymphatic endothelium.
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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.