ArticleInvestigative ophthalmology & visual science2017
Crosstalk Between Transforming Growth Factor Beta-2 and Toll-Like Receptor 4 in the Trabecular Meshwork.
Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 3 of them syntheses that pooled it.
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Who cites it
42 citing papers in PubMed, 3 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Association of Gene Polymorphisms with Normal Tension Glaucoma: A Systematic Review and Meta-Analysis.Genes · 2024Pooled it
- The association of toll-like receptor 4 gene polymorphisms with primary open angle glaucoma susceptibility: a meta-analysis.Bioscience reports · 2019Pooled it
- Associations between TLR4 Polymorphisms and Open Angle Glaucoma: A Meta-Analysis.BioMed research international · 2019Pooled it
- Novel Role for CGRP in Aqueous Humor Outflow.Investigative ophthalmology & visual science · 2026Article
- Glaucoma and Autoimmunity: Immunopathogenic Mechanisms and Emerging Immunomodulatory Therapies.Biomedicines · 2026Review
- Mechanistic Insights into Glucocorticoid-Induced Ocular Hypertension Using Differences in Mouse Strain Responsiveness.The American journal of pathology · 2026Article
- Integrin α4 and α9 in trabecular meshwork and Schlemm's canal function: emerging regulators of intraocular pressure homeostasis.Frontiers in cell and developmental biology · 2026Review
- Regulation of toll-like receptor signaling pathways in age-related eye disease: from mechanisms to targeted therapeutics.Inflammopharmacology · 2025Review
- TGFβ2 alters segmental outflow and ECM ultrastructure in the trabecular meshwork.Experimental eye research · 2025Article
- Peptide GTSFTTTAER FromFood science & nutrition · 2025Article
- The Inducible TGFβ2 Ocular Hypertension Mouse Model.Methods in molecular biology (Clifton, N.J.) · 2025Article
- From tumor microenvironment to ocular hypertension: unraveling the pathogenesis and therapeutic strategies of cancer-related glaucoma.Frontiers in medicine · 2025Review
- The Identification of New Pharmacological Targets for the Treatment of Glaucoma: A Network Pharmacology Approach.Pharmaceuticals (Basel, Switzerland) · 2024Article
- DAMPs Drive Fibroinflammatory Changes in the Glaucomatous ONH.Investigative ophthalmology & visual science · 2024Article
- The mechanics of the retina: Müller glia role on retinal extracellular matrix and modelling.Frontiers in medicine · 2024Review
- The Fibro-Inflammatory Response in the Glaucomatous Optic Nerve Head.International journal of molecular sciences · 2023Review
- Viral Vector-Induced Ocular Hypertension in Mice.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Decreased outflow facility and Schlemm's canal defects in a mouse model of glaucoma.Experimental eye research · 2022Article
- The application of lentiviral vectors for the establishment of TGFβ2-induced ocular hypertension in C57BL/6J mice.Experimental eye research · 2022Article
- A Novel Mouse Model of TGFβ2-Induced Ocular Hypertension Using Lentiviral Gene Delivery.International journal of molecular sciences · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Purpose: The trabecular meshwork (TM) is involved in the outflow of aqueous humor and intraocular pressure (IOP) regulation. Regulation of the extracellular matrix (ECM) by TGFβ2 signaling pathways in the TM has been extensively studied. Recent evidence has implicated toll-like receptor 4 (TLR4) in the regulation of ECM and fibrogenesis in liver, kidney, lung, and skin. Here, we investigated the role of TGFβ2-TLR4 signaling crosstalk in the regulation of the ECM in the TM and ocular hypertension. Methods: Cross sections of human donor eyes, primary human TM cells in culture, and dissected mouse TM rings were used to determine Tlr4 expression in the TM. Trabecular meshwork cells in culture were treated with TGFβ2 (5 ng/mL), TLR4 inhibitor (TAK-242, 15 μM), and a TLR4 ligand (cellular fibronectin isoform [cFN]-EDA). A/J (n = 13), AKR/J (n = 7), BALBc/J (n = 8), C3H/HeJ (n = 20), and C3H/HeOuJ (n = 10) mice were injected intravitreally with adenovirus 5 (Ad5).hTGFβ2c226s/c228s in one eye, with the uninjected contralateral eye serving as a control. Conscious IOP measurements were taken using a TonoLab rebound tonometer. Results: Toll-like receptor 4 is expressed in the human and mouse TM. Inhibition of TLR4 signaling in the presence of TGFβ2 decreases fibronectin expression. Activation of TLR4 by cFN-EDA in the presence of TGFβ2 further increases fibronectin, laminin, and collagen-1 expression, and TLR4 signaling inhibition blocks this effect. Ad5.hTGFβ2c226s/c228s induces ocular hypertension in wild-type mice but has no effect in Tlr4 mutant (C3H/HeJ) mice. Conclusions: These studies identify TGFβ2-TLR4 crosstalk as a novel pathway involved in ECM regulation in the TM and ocular hypertension. These data further explain the complex mechanisms involved in the development of glaucomatous TM damage.
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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.