ArticleInvestigative ophthalmology & visual science2014
Differential effects of caveolin-1 and -2 knockdown on aqueous outflow and altered extracellular matrix turnover in caveolin-silenced trabecular meshwork cells.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- The molecular mechanisms underlying retinal ganglion cell apoptosis and optic nerve regeneration in glaucoma (Review).International journal of molecular medicine · 2025Review
- Fibrosis-Related Gene and Protein Expression in Normal and Glaucomatous Trabecular Meshwork Cells.Investigative ophthalmology & visual science · 2025Article
- Molecular Mechanisms of Glaucoma Pathogenesis with Implications to Caveolin Adaptor Protein and Caveolin-Shp2 Axis.Aging and disease · 2024Review
- Comparative analysis of traction forces in normal and glaucomatous trabecular meshwork cells within a 3D, active fluid-structure interaction culture environment.Acta biomaterialia · 2024Article
- Elevated Intraocular Pressure and Glaucomatous Optic Neuropathy: Genes to Disease Mechanisms, Therapeutic Drugs, and Gene Therapies.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Thrombospondin 1 missense alleles induce extracellular matrix protein aggregation and TM dysfunction in congenital glaucoma.The Journal of clinical investigation · 2022Article
- Caveolar and non-Caveolar Caveolin-1 in ocular homeostasis and disease.Progress in retinal and eye research · 2022Review
- Matrix Metalloproteinases and Glaucoma.Biomolecules · 2022Review
- The physiological and pathophysiological roles of the autophagy lysosomal system in the conventional aqueous humor outflow pathway: More than cellular clean up.Progress in retinal and eye research · 2022Review
- A Role of Caveolae in Trabecular Meshwork Mechanosensing and Contractile Tone.Frontiers in cell and developmental biology · 2022Article
- Identification of Estrogen Signaling in a Prioritization Study of Intraocular Pressure-Associated Genes.International journal of molecular sciences · 2021Article
- Normal and glaucomatous outflow regulation.Progress in retinal and eye research · 2021Review
- Looking into the future: Gene and cell therapies for glaucoma.Veterinary ophthalmology · 2021Review
- Cathepsin B Localizes in the Caveolae and Participates in the Proteolytic Cascade in Trabecular Meshwork Cells. Potential New Drug Target for the Treatment of Glaucoma.Journal of clinical medicine · 2020Article
- Dexamethasone and Glucocorticoid-Induced Matrix Temporally Modulate Key Integrins, Caveolins, Contractility, and Stiffness in Human Trabecular Meshwork Cells.Investigative ophthalmology & visual science · 2020Article
- The MMP14-caveolin axis and its potential relevance for lipoedema.Nature reviews. Endocrinology · 2020Review
- Physiologic Consequences of Caveolin-1 Ablation in Conventional Outflow Endothelia.Investigative ophthalmology & visual science · 2020Article
- Primary open angle glaucoma genetics: The common variants and their clinical associations (Review).Molecular medicine reports · 2020Review
- Molecular taxonomy of human ocular outflow tissues defined by single-cell transcriptomics.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Myosin-X Silencing in the Trabecular Meshwork Suggests a Role for Tunneling Nanotubes in Outflow Regulation.Investigative ophthalmology & visual science · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeA single nucleotide polymorphism (SNP) identified between caveolin-1 (CAV1) and caveolin-2 (CAV2) on chromosome 7 is associated with glaucoma. One function of CAVs is endocytosis and recycling of extracellular matrix (ECM) components. Here, we generated CAV-silencing lentivirus to evaluate the effects on ECM turnover by trabecular meshwork (TM) cells and to measure the effect on outflow facility in anterior segment perfusion culture.
methodsShort hairpin CAV1 and CAV2 silencing and control lentivirus were generated, characterized, and applied to anterior segments in perfusion culture. Colocalization of CAVs with various ECM molecules in TM cells was investigated using immunofluorescence and confocal microscopy. Western immunoblotting and fluorogenic-based enzyme activity assays were used to investigate ECM protein levels and degradation, respectively.
resultsEndogenous CAVs colocalized with cortactin at podosome- or invadopodia-like structures (PILS), which are areas of focal ECM degradation. In perfusion culture, outflow rates increased significantly in CAV1-silenced anterior segments, whereas outflow significantly decreased in CAV2-silenced anterior segments. Matrix metalloproteinase (MMP)2 and MMP14, and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4) colocalized with both CAVs in TM cells. Protein levels and enzyme activities of MMP/ADAMTS4, fibronectin protein levels, actin stress fibers, and α-smooth muscle actin were all increased in CAV-silenced cells.
conclusionsCaveolin-mediated endocytosis is one mechanism by which TM cells can alter the physiological catabolism of ECM in order to change the composition of the outflow channels in the TM to regulate aqueous outflow resistance. Dysregulation of CAV function could contribute to the pathological changes in ECM that are observed in glaucoma.
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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.