May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
A Functional WNT Signaling Pathway in the Trabecular Meshwork That Regulates Intraocular Pressure
Author Affiliations & Notes
  • A. F. Clark
    Glaucoma Research, Alcon Research Ltd, Fort Worth, Texas
  • L. G. McNatt
    Glaucoma Research, Alcon Research Ltd, Fort Worth, Texas
  • P. E. Hellberg
    Glaucoma Research, Alcon Research Ltd, Fort Worth, Texas
  • J. C. Millar
    Glaucoma Research, Alcon Research Ltd, Fort Worth, Texas
  • J. S. Rubin
    Cellular & Molecular Biology, National Cancer Institute, Bethesda, Maryland
  • I.-H. Pang
    Glaucoma Research, Alcon Research Ltd, Fort Worth, Texas
  • W.-H. Wang
    Glaucoma Research, Alcon Research Ltd, Fort Worth, Texas
  • Footnotes
    Commercial Relationships A.F. Clark, E, E; L.G. McNatt, E, E; P.E. Hellberg, E, E; J.C. Millar, E, E; J.S. Rubin, None; I. Pang, E, E; W. Wang, E, E.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1142. doi:https://doi.org/
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    • Get Citation

      A. F. Clark, L. G. McNatt, P. E. Hellberg, J. C. Millar, J. S. Rubin, I.-H. Pang, W.-H. Wang; A Functional WNT Signaling Pathway in the Trabecular Meshwork That Regulates Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1142. doi: https://doi.org/.

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

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Abstract

Purpose:: To compare gene expression between normal and glaucomatous trabecular meshwork (TM) in order to identify novel signaling pathways involved in regulating intraocular pressure (IOP).

Methods:: Gene expression was compared using total RNA isolated from normal (n=6) and glaucomatous (n=6) cultured human TM cells. Differential gene expression was confirmed using QPCR. Western immunoblot and ELISA were used to determine protein differences. The effect of altered gene/protein expression on IOP was determined using perfusion cultured human anterior segments and viral expression vector transduction of mouse eyes.

Results:: Expression of the WNT signaling inhibitor sFRP1 was elevated in glaucomatous TM cells (5-fold increase in mRNA, p<0.01; 50% increase in protein, p<0.05). Human TM cells express various components of the WNT signaling system, including WNTs 2b, 5a, 5b and FZD 1,2,6,7. Increased sFRP1 caused decreased levels of the WNT signaling intermediate ß-catenin in the TM of perfusion cultured eyes (p<0.05) as well as in cultured TM cells. Recombinant sFRP1 significantly decreased the aqueous outflow facility in perfusion cultured human eyes (40-60% decrease, n=4, p<0.05). Transduction of mouse eyes with Ad5.sFRP1 significantly elevated IOP (2-fold increase, p<0.05). There was a positive correlation between anterior segment sFRP1 expression and level of IOP elevation (r2=0.81).

Conclusions:: The TM contains a functional WNT signaling pathway. Perturbation of the WNT signaling pathway by the WNT inhibitor sFRP1 leads to elevated IOP, which may play a role in glaucoma pathogenesis.

Keywords: trabecular meshwork • intraocular pressure • gene/expression 
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