ArticleThe Journal of clinical investigation2014
Targeting VE-PTP activates TIE2 and stabilizes the ocular vasculature.
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 128 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
128 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 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
- Tie2 protects the vasculature against thrombus formation in systemic inflammation.The Journal of clinical investigation · 2018Trial
- Pro-permeability Factors in Diabetic Macular Edema; the Diabetic Macular Edema Treated With Ozurdex Trial.American journal of ophthalmology · 2016Trial
- Angiogenic Doping: Plausible Yet Difficult to Detect.Sports medicine (Auckland, N.Z.) · 2026Review
- Review
- Targeting CD148 for Antithrombotic Therapy: Functional and Molecular Evaluation of AKB-9778.Pharmacology research & perspectives · 2026Article
- Disrupting VE-cadherin Y685 phosphorylation inhibits development of experimental diabetic and prediabetic retinopathy.The Journal of clinical investigation · 2026Article
- Molecular stress and neurovascular injury in the diabetic retina.The Journal of clinical investigation · 2026Review
- A Highly Active Angiopoietin 1 Mimetic Potentiates Angiogenesis in Mouse Models of Choroidal Neovascularization.Translational vision science & technology · 2026Article
- The stroke risk gene Foxf2 maintains brain endothelial cell function via Tie2 signaling.Nature neuroscience · 2026Article
- Mechanisms That Prevent Vascular Leakage During Leukocyte Extravasation.Acta physiologica (Oxford, England) · 2025Review
- Plasmodium falciparum impairs Ang-1 secretion by pericytes in a 3D brain microvessel model.EMBO molecular medicine · 2025Article
- Dual VEGF-Targeting Strategy Via AAV2-Delivered sFLT-1 and shVEGF for Retinal Neovascularization Therapy.Investigative ophthalmology & visual science · 2025Article
- Bispecific receptor decoy proteins block ocular neovascularization via simultaneous blockade of vascular endothelial growth factor A and C.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Promoting vascular stability through Src inhibition and Tie2 activation: A model-based analysis.iScience · 2025Article
- Review
- The Ever-Expanding Influence of the Endothelial Nitric Oxide Synthase.Basic & clinical pharmacology & toxicology · 2025Review
- Razuprotafib Does Not Improve Microcirculatory Perfusion Disturbances nor Renal Edema in Rats on Extracorporeal Circulation.International journal of molecular sciences · 2025Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
Retinal and choroidal neovascularization (NV) and vascular leakage contribute to visual impairment in several common ocular diseases. The angiopoietin/TIE2 (ANG/TIE2) pathway maintains vascular integrity, and negative regulators of this pathway are potential therapeutic targets for these diseases. Here, we demonstrated that vascular endothelial-protein tyrosine phosphatase (VE-PTP), which negatively regulates TIE2 activation, is upregulated in hypoxic vascular endothelial cells, particularly in retinal NV. Intraocular injection of an anti-VE-PTP antibody previously shown to activate TIE2 suppressed ocular NV. Furthermore, a small-molecule inhibitor of VE-PTP catalytic activity (AKB-9778) activated TIE2, enhanced ANG1-induced TIE2 activation, and stimulated phosphorylation of signaling molecules in the TIE2 pathway, including AKT, eNOS, and ERK. In mouse models of neovascular age-related macular degeneration, AKB-9778 induced phosphorylation of TIE2 and strongly suppressed NV. Ischemia-induced retinal NV, which is relevant to diabetic retinopathy, was accentuated by the induction of ANG2 but inhibited by AKB-9778, even in the presence of high levels of ANG2. AKB-9778 also blocked VEGF-induced leakage from dermal and retinal vessels and prevented exudative retinal detachments in double-transgenic mice with high expression of VEGF in photoreceptors. These data support targeting VE-PTP to stabilize retinal and choroidal blood vessels and suggest that this strategy has potential for patients with a wide variety of retinal and choroidal vascular diseases.
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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.