ArticleInvestigative ophthalmology & visual science2013
Overexpression of SPARC in human trabecular meshwork increases intraocular pressure and alters extracellular matrix.
Article in Investigative ophthalmology & visual science, 2013. 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, 58 citations in OpenAlex.
- Integrin-Linked Kinase Suppression Reduces SPARC's Effect on Intraocular Pressure and Extracellular Matrix.Investigative ophthalmology & visual science · 2026Article
- Association of Matrix Metalloproteinases Polymorphisms with Glaucoma Risk, Glaucoma Phenotype, and Response to Treatment with Selective Laser Trabeculoplasty or Latanoprost.International journal of molecular sciences · 2024Article
- Digital spatial profiling of segmental outflow regions in trabecular meshwork reveals a role for ADAM15.PloS one · 2024Article
- The Extracellular Matrix: Its Composition, Function, Remodeling, and Role in Tumorigenesis.Biomimetics (Basel, Switzerland) · 2023Review
- Review
- Genome-Wide RNA Sequencing of Human Trabecular Meshwork Cells Treated with TGF-β1: Relevance to Pseudoexfoliation Glaucoma.Biomolecules · 2022Article
- Effect of SPARC Suppression in Mice, Perfused Human Anterior Segments, and Trabecular Meshwork Cells.Investigative ophthalmology & visual science · 2022Article
- Sodium 4-Phenylbutyrate Reduces Ocular Hypertension by Degrading Extracellular Matrix Deposition via Activation of MMP9.International journal of molecular sciences · 2021Article
- Diverse effects of pan-ROCK and ROCK2 inhibitors on 2 D and 3D cultured human trabecular meshwork (HTM) cells treated with TGFβ2.Scientific reports · 2021Article
- C3 Transferase-Expressing scAAV2 Transduces Ocular Anterior Segment Tissues and Lowers Intraocular Pressure in Mouse and Monkey.Molecular therapy. Methods & clinical development · 2020Article
- Wnt Activation After Inhibition Restores Trabecular Meshwork Cells Toward a Normal Phenotype.Investigative ophthalmology & visual science · 2020Article
- The extracellular matrix in development.Development (Cambridge, England) · 2020Review
- TGFβ2-Hepcidin Feed-Forward Loop in the Trabecular Meshwork Implicates Iron in Glaucomatous Pathology.Investigative ophthalmology & visual science · 2020Article
- Secreted protein acidic and rich in cysteine (SPARC) knockout mice have greater outflow facility.PloS one · 2020Article
- Fidelity of long-term cryopreserved adipose-derived stem cells for differentiation into cells of ocular and other lineages.Experimental eye research · 2019Article
- Prion protein modulates endothelial to mesenchyme-like transition in trabecular meshwork cells: Implications for primary open angle glaucoma.Scientific reports · 2019Article
- Vertebrate Lonesome Kinase Regulated Extracellular Matrix Protein Phosphorylation, Cell Shape, and Adhesion in Trabecular Meshwork Cells.Journal of cellular physiology · 2017Article
- Segmental outflow of aqueous humor in mouse and human.Experimental eye research · 2017Review
- Gene transfer to the outflow tract.Experimental eye research · 2017Review
- Aberrant Collagen Composition of the Trabecular Meshwork Results in Reduced Aqueous Humor Drainage and Elevated IOP in MMP-9 Null Mice.Investigative ophthalmology & visual science · 2016Article
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeIntraocular pressure (IOP) regulation is largely unknown. SPARC-null mice demonstrate a lower IOP resulting from increased outflow. SPARC is a matricellular protein often associated with fibrosis. We hypothesized that SPARC overexpression would alter IOP by affecting extracellular matrix (ECM) synthesis and/or turnover in the trabecular meshwork (TM).
methodsAn adenoviral vector containing human SPARC was used to increase SPARC expression in human TM endothelial cells and perfused human anterior segments using multiplicities of infection (MOIs) 25 or 50. Total RNA from TM was used for quantitative PCR, while protein from cell lysates and conditioned media were used for immunoblot analyses and zymography. After completion of perfusion, the anterior segments were fixed, sectioned, and examined by light and confocal microscopy.
resultsSPARC overexpression increased the IOP of perfused human anterior segments. Fibronectin and collagens IV and I protein levels were elevated in both TM cell cultures and within the juxtacanalicular (JCT) region of perfused anterior segments. Collagen VI and laminin protein levels were increased in TM cell cultures but not in perfused anterior segments. The protein levels of pro-MMP-9 decreased while the kinetic inhibitors of metalloproteinases, TIMP-1 and PAI-1 protein levels, increased at MOI 25. At MOI 50, the protein levels of pro-MMP-1, -3, and -9 also decreased while PAI-1 and TIMP-1 and -3 increased. Only MMP-9 activity was decreased on zymography. mRNA levels of the collagens, fibronectin, and laminin were not affected by SPARC overexpression.
conclusionsSPARC overexpression increases IOP in perfused cadaveric human anterior segments resulting from a qualitative change the JCT ECM. Selective decrease of MMP-9 activity is likely part of the mechanism. SPARC is a regulatory node for IOP.
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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.