ArticleInvestigative ophthalmology & visual science2014
TGF-β2-mediated ocular hypertension is attenuated in SPARC-null mice.
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 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Integrin-Linked Kinase Suppression Reduces SPARC's Effect on Intraocular Pressure and Extracellular Matrix.Investigative ophthalmology & visual science · 2026Article
- Pro-Homeostatic Effects of Estrogen on Intraocular Pressure and the Trabecular Meshwork.Investigative ophthalmology & visual science · 2026Article
- Review
- SPARC: a potential target for functional nanomaterials and drugs.Frontiers in molecular biosciences · 2023Review
- A Novel Mouse Model of TGFβ2-Induced Ocular Hypertension Using Lentiviral Gene Delivery.International journal of molecular sciences · 2022Article
- Atorvastatin reduces IOP in ocular hypertensionInternational journal of molecular medicine · 2022Article
- Effect of SPARC Suppression in Mice, Perfused Human Anterior Segments, and Trabecular Meshwork Cells.Investigative ophthalmology & visual science · 2022Article
- Downregulation of secreted protein acidic and rich in cysteine in human trabecular meshwork cells.Experimental and therapeutic medicine · 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
- Generating cell-derived matrices from human trabecular meshwork cell cultures for mechanistic studies.Methods in cell biology · 2020Article
- Secreted protein acidic and rich in cysteine (SPARC) knockout mice have greater outflow facility.PloS one · 2020Article
- Aqueous humor levels of TGFβ2 and SFRP1 in different types of glaucoma.BMC ophthalmology · 2019Article
- Inhibitory role of transforming growth factor β2 in experimental autoimmune anterior uveitis.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2019Article
- TGF-β-induced IOP elevations are mediated by RhoA in the early but not the late fibrotic phase of open angle glaucoma.Molecular vision · 2018Article
- Multiplex Cytokine Analysis of Aqueous Humor in Juvenile Idiopathic Arthritis-Associated Anterior Uveitis With or Without Secondary Glaucoma.Frontiers in immunology · 2018Article
- Rho GTPase signaling promotes constitutive expression and release of TGF-β2 by human trabecular meshwork cells.Experimental eye research · 2016Article
- Elevation of intraocular pressure in rodents using viral vectors targeting the trabecular meshwork.Experimental eye research · 2015Review
- The Thrombospondin1-TGF-β Pathway and Glaucoma.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2015Article
- Secreted Protein Acidic and Rich in Cysteine in Ocular Tissue.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2015Review
- Recent Developments in Understanding the Role of Aqueous Humor Outflow in Normal and Primary Open Angle Glaucoma.Current ophthalmology reports · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTransforming growth factor-β2 (TGF-β2) has been implicated in the pathogenesis of primary open-angle glaucoma through extracellular matrix (ECM) alteration among various mechanisms. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates ECM within the trabecular meshwork (TM), and is highly upregulated by TGF-β2. We hypothesized that, in vivo, SPARC is a critical regulatory node in TGF-β2-mediated ocular hypertension.
methodsEmpty (Ad.empty) or TGF-β2-containing adenovirus (Ad.TGF-β2) was injected intravitreally into C57BL6-SV129 WT and SPARC-null mice. An initial study was performed to identify a stable period for IOP measurement under isoflurane. The IOP was measured before injection and every other day for two weeks using rebound tonometry. Additional mice were euthanized at peak IOP for immunohistochemistry.
resultsThe IOP was stable under isoflurane during minutes 5 to 8. The IOP was significantly elevated in Ad.TGF-β2-injected (n = 8) versus Ad.empty-injected WT (n = 8) mice and contralateral uninjected eyes during days 4 to 11 (P < 0.03). The IOPs were not significantly elevated in Ad.TGF-β2-injected versus Ad.empty-injected SPARC-null mice. However, on day 8, the IOP of Ad.TGF-β2-injected SPARC-null eyes was elevated compared to that of contralateral uninjected eyes (P = 0.0385). Immunohistochemistry demonstrated that TGF-β2 stimulated increases in collagen IV, fibronectin, plasminogen activator inhibitor-1 (PAI-1), connective tissue growth factor (CTGF), and SPARC in WT mice, but only PAI-1 and CTGF in SPARC-null mice (P < 0.05).
conclusionsSPARC is essential to the regulation of TGF-β2-mediated ocular hypertension. Deletion of SPARC significantly attenuates the effects of TGF-β2 by restricting collagen IV and fibronectin expression. These data provide further evidence that SPARC may have an important role in IOP regulation and possibly glaucoma pathogenesis.
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