ArticleBlood2013
Soluble vascular endothelial growth factor receptor 3 is essential for corneal alymphaticity.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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.
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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
42 citing papers in PubMed, 89 citations in OpenAlex.
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- The Impact of Modern Industrialized Dietary Sodium Intake on the Plasma Proteome.American journal of hypertension · 2026Article
- Limbal Epithelial Stem Cells in Review: Immune and Lymphangiogenic Privilege and Their Clinical Relevance.Cells · 2026Review
- VEGF-D Dependent IFNγ Production by Natural Killer Cells in Lymphangioleiomyomatosis.Journal of cellular immunology · 2025Article
- Soluble FLT-1 in angiogenesis: pathophysiological roles and therapeutic implications.Angiogenesis · 2024Review
- The Alzheimer's disease-linked protease BACE2 cleaves VEGFR3 and modulates its signaling.The Journal of clinical investigation · 2024Article
- Lymphangiogenesis Guidance Mechanisms and Therapeutic Implications in Pathological States of the Cornea.Cells · 2023Review
- Vascular endothelial growth factor-C in activating vascular endothelial growth factor receptor-3 and chemokine receptor-4 in melanoma adhesion.Journal of cellular and molecular medicine · 2022Review
- Cystathionine β-synthase as novel endogenous regulator of lymphangiogenesis via modulating VEGF receptor 2 and 3.Communications biology · 2022Article
- Ocular Lymphatic and Glymphatic Systems: Implications for Retinal Health and Disease.International journal of molecular sciences · 2022Review
- Osteopontin contributes to virus resistance associated with type I IFN expression, activation of downstream ifn-inducible effector genes, and CCR2Frontiers in immunology · 2022Article
- Corneal Lymphangiogenesis: Current Pathophysiological Understandings and Its Functional Role in Ocular Surface Disease.International journal of molecular sciences · 2021Review
- The physiological and pathological functions of VEGFR3 in cardiac and lymphatic development and related diseases.Cardiovascular research · 2021Review
- Review
- Review
- Roles of Epithelial and Mesenchymal TRP Channels in Mediating Inflammatory Fibrosis.Frontiers in immunology · 2021Review
- Macrophage-Mediated Tissue Vascularization: Similarities and Differences Between Cornea and Skin.Frontiers in immunology · 2021Review
- Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy.Biomolecules · 2020Review
- Role of Endogenous Regulators of Hem- And Lymphangiogenesis in Corneal Transplantation.Journal of clinical medicine · 2020Review
- Biomaterials for Modulating Lymphatic Function in Immunoengineering.ACS pharmacology & translational science · 2019Review
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Corneal transparency is a prerequisite for optimal vision and in turn relies on an absence of blood and lymphatic vessels, which is remarkable given the cornea's proximity to vascularized tissues. Membrane-bound vascular endothelial growth factor receptor 3 (VEGFR-3), with its cognate ligand vascular endothelial growth factor C (VEGF-C), is a major mediator of lymphangiogenesis. Here, we demonstrate that the cornea expresses a novel truncated isoform of this molecule, soluble VEGFR-3 (sVEGFR-3), which is critical for corneal alymphaticity, by sequestering VEGF-C. sVEGFR-3 binds and sequesters VEGF-C, thereby blocking signaling through VEGFR-3 and suppressing lymphangiogenesis induced by VEGF-C. sVEGFR-3 knockdown leads to lymphangiogenesis and hemangiogenesis in the mouse cornea, while overexpression of sVEGFR-3 inhibits lymphangiogenesis and hemangiogenesis in a murine suture injury model. Pax6(+/-) mice spontaneously develop corneal and lymphatic vessels and are deficient in sVEGFR-3. sVEGFR-3 suppresses hemangiogenesis by blocking VEGF-C-induced phosphorylation of VEGFR-2. Overexpression of sVEGFR-3 leads to a 5-fold increase in corneal transplant survival in mouse models. sVEGFR-3 holds promise as a molecule to control and regress lymphatic-vessel-based dysfunction. Therefore, sVEGFR-3 has the potential to protect the injured cornea from opacification secondary to infection, inflammation, or transplant rejection.
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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.