ArticleInvestigative ophthalmology & visual science2020
Wnt Activation After Inhibition Restores Trabecular Meshwork Cells Toward a Normal Phenotype.
Article in Investigative ophthalmology & visual science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- The Hippo signalling pathway and its impact on eye diseases.Journal of cellular and molecular medicine · 2024Pooled it
- Correlation of autoantibody profiles with clinical parameters in exfoliative glaucoma patients.International ophthalmology · 2025Article
- Divergence in cellular markers observed in single-cell transcriptomics datasets between cultured primary trabecular meshwork cells and tissues.Scientific data · 2025Article
- Mechanobiology in the eye.npj biological physics and mechanics · 2025Review
- Genetic susceptibility to schizophrenia through neuroinflammatory pathways associated with retinal thinness.Nature. Mental health · 2025Article
- Influence of dexamethasone-induced matrices on the TM transcriptome.Experimental eye research · 2024Article
- The role of YAP/TAZ mechanosignaling in trabecular meshwork and Schlemm's canal cell dysfunction.Vision research · 2024Review
- GSK3β Inhibitors Inhibit TGFβ Signaling in the Human Trabecular Meshwork.Investigative ophthalmology & visual science · 2024Article
- Article
- To be or not to be - Decoding the Trabecular Meshwork Cell Identity.bioRxiv : the preprint server for biology · 2024Article
- Squishy matters - Corneal mechanobiology in health and disease.Progress in retinal and eye research · 2024Review
- Targeting YAP/TAZ mechanosignaling to ameliorate stiffness-induced Schlemm's canal cell pathobiology.American journal of physiology. Cell physiology · 2024Article
- Targeting YAP mechanosignaling to ameliorate stiffness-induced Schlemm's canal cell pathobiology.bioRxiv : the preprint server for biology · 2023Article
- Simvastatin Attenuates Glucocorticoid-Induced Human Trabecular Meshwork Cell Dysfunction via YAP/TAZ Inactivation.Current eye research · 2023Article
- High VEGF Concentrations Accelerate Human Trabecular Meshwork Fibrosis in a TAZ-Dependent Manner.International journal of molecular sciences · 2023Article
- Dexamethasone Modulates the Dynamics of Wnt Signaling in Human Trabecular Meshwork Cells.Vision (Basel, Switzerland) · 2023Article
- Ocular Biomechanics and Glaucoma.Vision (Basel, Switzerland) · 2023Review
- Article
- Extracellular-Matrix Mechanics Regulate the Ocular Physiological and Pathological Activities.Journal of ophthalmology · 2023Review
- Endogenous expression of Notch pathway molecules in human trabecular meshwork cells.Experimental eye research · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Purpose: Wnt is a spatiotemporally regulated signaling pathway whose inhibition is associated with glaucoma, elevated intraocular pressure (IOP), and cell stiffening. Whether such changes are permanent or may be reversed is unclear. Here, we determine if activation of Wnt pathway after inhibition reverses the pathologic phenotype. Methods: Primary human trabecular meshwork (hTM) cells from nonglaucomatous donors were cultured for 12 days in the absence or presence of Wnt modulators: (i) LGK974 (Porcn inhibitor, 10 µM); (ii) LY2090314 (pGSK3β inhibitor, 250 nM); or (iii) 9 days of LGK974 followed by 3 days of LY2090314. Wnt modulation were determined by Western blotting and extracellular matrix (ECM) related genes were evaluated by quantitative PCR. Cytoskeletal morphology was determined by immunofluorescence and cell stiffness by atomic force microscopy. Results: Wnt activation was confirmed by downregulation of pGSK3β (0.3-fold; P < 0.01), overexpression of AXIN2 (6.7-fold; P < 0.001), and LEF1 (3.8-fold; P < 0.001). Wnt inhibition resulted in dramatic changes in F-actin, which were resolved with subsequent Wnt activation. Concurrently, cell stiffness that was elevated with Wnt inhibition (11.86 kPa; P < 0.01) decreased with subsequent Wnt activation (4.195 kPa; P < 0.01) accompanied by significant overexpression of phosphorylated YAP (1.8-fold; P < 0.001) and TAZ (1.4-fold; P < 0.001). Additionally, Wnt activation after inhibition significantly repressed ECM genes (SPARC and CTGF, P < 0.01), cross-linking genes (LOX and TGM2, P < 0.05), inhibitors of matrix metalloproteinases (TIMP1 and PAI1, P < 0.001), and overexpressed MMP 1/9/14 (P < 0.01). Conclusions: These data strongly demonstrate that, in normal hTM cells, activation of the Wnt pathway reverses the pathological phenotype caused by Wnt inhibition and may thus be a viable therapeutic for lowering IOP.
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