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Differential effects of prostaglandin E2-sensitive receptors on contractility of human ocular cells that regulate conventional outflow.

Publication ,  Journal Article
Wang, JW; Woodward, DF; Stamer, WD
Published in: Invest Ophthalmol Vis Sci
July 16, 2013

PURPOSE: The goal of this study was to functionally compare prostaglandin E2 (PGE2)-sensitive receptors in human primary cells involved in conventional outflow. METHODS: The expression profile of prostaglandin (PG) receptors in primary cultures of human trabecular meshwork (TM) and Schlemm's canal (SC) cells were determined by quantitative-PCR. The functional activities of endogenous PGE2-sensitive receptors were evaluated using subtype-selective agonists and antagonists with cell impedance technology. RESULTS: Agonist-sensitive EP1, EP2, and EP4 receptors were present in TM cells, all increasing cell stiffness (or contractility) in a dose-dependent manner. Rank order of efficacy (Emax) for agonists in TM cells were EP1 greater than EP2 greater than EP4 with EC50 1.1 μM, 0.56 μM, and 0.1 μM, respectively, and no functional EP3 receptors were found. Of the four EP receptor subtypes active in SC cells, EP1 and EP3 receptor activation increased cell stiffness, while EP2 and EP4 agonists dose-dependently decreased cell stiffness 47% and 23% with EC50 values of 170 nM and 69 nM, respectively. Consistent with these observations, the Rho kinase inhibitor Y-27632 decreased cell impedance (stiffness) of TM and SC cells (∼60%), while Rho GTPase activator thrombin caused cell impedance to increase in both cell types (168%-190%). CONCLUSIONS: Cell impedance positively correlates with cellular stiffness/contractility. Because EP2/4 receptors caused decreased cell stiffness in SC, but not in TM cells, both receptors appear to mediate IOP lowering via changes in SC cell stiffness in the conventional outflow pathway.

Duke Scholars

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

July 16, 2013

Volume

54

Issue

7

Start / End Page

4782 / 4790

Location

United States

Related Subject Headings

  • Trabecular Meshwork
  • Receptors, Prostaglandin
  • Pyridines
  • Polymerase Chain Reaction
  • Ophthalmology & Optometry
  • Humans
  • Enzyme Inhibitors
  • Elasticity
  • Dinoprostone
  • Cells, Cultured
 

Citation

APA
Chicago
ICMJE
MLA
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Wang, J. W., Woodward, D. F., & Stamer, W. D. (2013). Differential effects of prostaglandin E2-sensitive receptors on contractility of human ocular cells that regulate conventional outflow. Invest Ophthalmol Vis Sci, 54(7), 4782–4790. https://doi.org/10.1167/iovs.13-12363
Wang, Jenny W., David F. Woodward, and W Daniel Stamer. “Differential effects of prostaglandin E2-sensitive receptors on contractility of human ocular cells that regulate conventional outflow.Invest Ophthalmol Vis Sci 54, no. 7 (July 16, 2013): 4782–90. https://doi.org/10.1167/iovs.13-12363.
Wang, Jenny W., et al. “Differential effects of prostaglandin E2-sensitive receptors on contractility of human ocular cells that regulate conventional outflow.Invest Ophthalmol Vis Sci, vol. 54, no. 7, July 2013, pp. 4782–90. Pubmed, doi:10.1167/iovs.13-12363.
Wang JW, Woodward DF, Stamer WD. Differential effects of prostaglandin E2-sensitive receptors on contractility of human ocular cells that regulate conventional outflow. Invest Ophthalmol Vis Sci. 2013 Jul 16;54(7):4782–4790.

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

July 16, 2013

Volume

54

Issue

7

Start / End Page

4782 / 4790

Location

United States

Related Subject Headings

  • Trabecular Meshwork
  • Receptors, Prostaglandin
  • Pyridines
  • Polymerase Chain Reaction
  • Ophthalmology & Optometry
  • Humans
  • Enzyme Inhibitors
  • Elasticity
  • Dinoprostone
  • Cells, Cultured