ArticleInvestigative ophthalmology & visual science2015
Gremlin Induces Ocular Hypertension in Mice Through Smad3-Dependent Signaling.
Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Knock-Down of Glucocorticoid Receptor Beta (GRβ) Enhances the Ocular Hypertensive Response to Dexamethasone in C57BL/6J Mice.International journal of molecular sciences · 2026Article
- TGFβ2 alters segmental outflow and ECM ultrastructure in the trabecular meshwork.Experimental eye research · 2025Article
- Profiling IOP-Responsive Genes in the Trabecular Meshwork and Optic Nerve Head in a Rat Model of Controlled Elevation of Intraocular Pressure.Investigative ophthalmology & visual science · 2024Article
- A ROCK inhibitor suppresses the transforming growth factor-beta-2-induced endothelial-mesenchymal transition in Schlemm's canal endothelial cells.Scientific reports · 2023Article
- A method describing the microdissection of trabecular meshwork tissue from Brown Norway rat eyes.Experimental eye research · 2023Article
- CCN2/CTGF tip the balance of growth factors towards TGF-β2 in primary open-angle glaucoma.Frontiers in molecular biosciences · 2023Article
- Viral Vector-Induced Ocular Hypertension in Mice.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Fibronectin extra domain A (FN-EDA) causes glaucomatous trabecular meshwork, retina, and optic nerve damage in mice.Cell & bioscience · 2022Article
- Consensus Recommendation for Mouse Models of Ocular Hypertension to Study Aqueous Humor Outflow and Its Mechanisms.Investigative ophthalmology & visual science · 2022Review
- αVβ8 integrin targeting to prevent posterior capsular opacification.JCI insight · 2021Article
- ID1 and ID3 are Negative Regulators of TGFβ2-Induced Ocular Hypertension and Compromised Aqueous Humor Outflow Facility in Mice.Investigative ophthalmology & visual science · 2021Article
- Fibronectin has multifunctional roles in posterior capsular opacification (PCO).Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Fibronectin extra domain A (FN-EDA) elevates intraocular pressure through Toll-like receptor 4 signaling.Scientific reports · 2020Article
- Inducible rodent models of glaucoma.Progress in retinal and eye research · 2020Review
- Nuclear factor-kappa beta signaling is required for transforming growth factor Beta-2 induced ocular hypertension.Experimental eye research · 2020Article
- Gremlin is a potential target for posterior capsular opacification.Cell cycle (Georgetown, Tex.) · 2019Article
- BMP and Activin Membrane Bound Inhibitor Regulates the Extracellular Matrix in the Trabecular Meshwork.Investigative ophthalmology & visual science · 2018Article
- Glucocorticoid receptor GRβ regulates glucocorticoid-induced ocular hypertension in mice.Scientific reports · 2018Article
- The many faces of the trabecular meshwork cell.Experimental eye research · 2017Review
- Crosstalk Between Transforming Growth Factor Beta-2 and Toll-Like Receptor 4 in the Trabecular Meshwork.Investigative ophthalmology & visual science · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTransforming growth factor-β2 induces extracellular matrix (ECM) remodeling, which likely contributes to the defective function of the trabecular meshwork (TM) leading to glaucomatous ocular hypertension. Bone morphogenetic proteins (BMPs) inhibit these profibrotic effects of TGFβ2. The BMP antagonist gremlin is elevated in glaucomatous TM cells and increases IOP in an ex vivo perfusion culture model. The purpose of this study was to determine whether gremlin regulates ECM proteins in the TM, signals through the Smad3-dependent pathway, and induces ocular hypertension in mice.
methodsAd5.Gremlin or Ad5.TGFβ2 was injected intravitreally into one eye of each mouse. Intraocular pressure measurements were taken using a TonoLab tonometer. Gremlin, TGFβ2, fibronectin (FN), and collagen-1 (Col-1) expression in the TM was determined by immunofluorescence, Western immunoblot, and quantitative (q)PCR analyses.
resultsAd5.Gremlin or Ad5.TGFβ2 each caused significant IOP elevation in mice. Immunofluorescence and Western blot analysis demonstrated that gremlin and TGFβ2 reciprocally increased the expression of each other, and both increased FN expression in the TM and surrounding tissues. Ad5.Gremlin elevated IOP and increased Fn and Col-1 gene expression in the TM of Smad3 wild-type (WT) mice, but had no effect in Smad3 HET or Smad3 KO mice.
conclusionsOur results demonstrate that intravitreal injections of either Ad5.Gremlin or Ad5.TGFβ2 elevate IOP and upregulate the ECM protein FN in the TM of mice. These data show that gremlin signals through the Smad3-dependent pathway in the TM to elevate IOP. We determined for the first time gremlin's role in inducing ocular hypertension in an in vivo model system.
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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.