May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
TGFß2–Induced Changes in Trabecular Meshwork Matrix Component Expression: Implications for Intraocular Pressure
Author Affiliations & Notes
  • D.L. Fleenor
    Glaucoma Research, Alcon Research Ltd, Fort Worth, TX
  • A. Shepard
    Glaucoma Research, Alcon Research Ltd, Fort Worth, TX
  • P. Hellberg
    Glaucoma Research, Alcon Research Ltd, Fort Worth, TX
  • N. Jacobson
    Glaucoma Research, Alcon Research Ltd, Fort Worth, TX
  • I.–H. Pang
    Glaucoma Research, Alcon Research Ltd, Fort Worth, TX
  • A. Clark
    Glaucoma Research, Alcon Research Ltd, Fort Worth, TX
  • Footnotes
    Commercial Relationships  D.L. Fleenor, Alcon Research Ltd. E; A. Shepard, Alcon Research Ltd. E; P. Hellberg, Alcon Research Ltd. E; N. Jacobson, Alcon Research Ltd. E; I. Pang, Alcon Research Ltd. E; A. Clark, Alcon Research Ltd. E.
  • Footnotes
    Support  Alcon Research Ltd.
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 3774. doi:
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      D.L. Fleenor, A. Shepard, P. Hellberg, N. Jacobson, I.–H. Pang, A. Clark; TGFß2–Induced Changes in Trabecular Meshwork Matrix Component Expression: Implications for Intraocular Pressure . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3774.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Excess extracellular matrix (ECM) material is believed to contribute to glaucoma etiology via increased resistance through the trabecular meshwork (TM) region. Transforming growth factor–ß2 (TGFß2) is known to modulate expression of a variety of ECM molecules, therefore we investigated its effects on human TM cell cultures and perfused ocular tissues. Methods: Human TM cells were treated with TGFß2 and/or other test agents, followed by ELISA analysis of culture supernatants for secreted fibronectin. Total RNA was isolated from pooled TM cell monolayers and used for Affymetrix microarray analysis. TGFß2 was also evaluated for intraocular pressure (IOP) effects in a perfused organ culture (POC) model using human anterior segments and POC eluates were analyzed for fibronectin content. Results: Average basal fibronectin secretion from TM cells was 1.6–53.5 µg/mL/24 h, depending upon cell line and passage number. TM cell fibronectin secretion was stimulated in a time– and dose–dependent manner by TGFß2. At 5 ng/mL TGFß2 increased GTM–3 fibronectin secretion 11 ± 2 fold. In the POC model, TGFß2 (5 ng/mL) treatment elevated IOP (155 ± 19% at Day 3, n = 5), as well as increased eluate fibronectin content (9.9 ± 3.0 fold). Overnight treatment of TM cells with TGFß2 (5 ng/mL) resulted in > 2 fold upregulation of more than 40 ECM–related genes, such as collagen IVα and Vα, and chondroitin sulfate proteoglycan 2. Conclusions: TGFß2 effects on IOP may be transduced via changes in TM ECM composition. Modulation of TGFß2–induced changes in ECM, such as fibronectin secretion, may provide a novel and viable therapeutic approach to the management of glaucoma. [Supported by Alcon Research, Ltd.]

Keywords: trabecular meshwork • extracellular matrix • outflow: trabecular meshwork 
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