April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Prostaglandin EP4 Receptor Activation Increases Outflow Facility in Perfused Human Eyes
Author Affiliations & Notes
  • L. H. Millard
    Pharmacology,
    University of Arizona, Tucson, Arizona
  • D. F. Woodward
    Bioll Sci RD-2C, Allergan, Inc, Irvine, California
  • W. D. Stamer
    Ophthalmology,
    University of Arizona, Tucson, Arizona
  • Footnotes
    Commercial Relationships  L.H. Millard, None; D.F. Woodward, Allergan, Inc., E; W.D. Stamer, Allergan, Inc., F.
  • Footnotes
    Support  Allergan
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 151. doi:https://doi.org/
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      L. H. Millard, D. F. Woodward, W. D. Stamer; Prostaglandin EP4 Receptor Activation Increases Outflow Facility in Perfused Human Eyes. Invest. Ophthalmol. Vis. Sci. 2010;51(13):151. doi: https://doi.org/.

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

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Abstract

Introduction: : Lindsey H. Millard, David F. Woodward and W. Daniel Stamer

Purpose: : Prostaglandin EP4 receptors are expressed by many human ocular tissues including both trabecular meshwork (TM) and Schlemm’s canal (SC) cells of the conventional outflow pathway. Activation of EP4 receptors in monkey eyes efficaciously lowers intraocular pressure, while having no effect on aqueous humor secretion or uveoscleral outflow. We hypothesize that prostaglandin EP4 receptors regulate human conventional outflow.

Methods: : Paired post-mortem human eyes were received within 24 hours, prepared for organ-culture and were perfused at 8 mmHg constant pressure. After establishing a stable baseline, anterior chamber contents were exchanged with either drug (10 nM 3,7 dithia PGE1) or media (control). After 4 hours, eyes were perfused-fixed with 4% PFA at 8 mmHg for 30 min. Corneo-scleral region of eyes were embedded in plastic, sectioned and stained with toluidine blue.

Results: : Baseline outflow facility for control (0.19±0.067 ul/min/mmHg; mean ±SEM) and drug-treated eyes (0.21±0.02 ul/min/mmHg) were similar. Outflow facility increased by 51±18% over baseline levels in drug-treated eyes after exchange (n=6 eyes; p=0.005). When compared to contralateral eyes, outflow facility in drug treated eyes increased by 69±23% (p<0.01). Histological analysis of perfused eyes showed no gross abnormalities in tissue architecture or discernable differences in cell abundance or morphology.

Conclusions: : Results suggest that the EP4 receptor activation significantly increases outflow facility in human eyes in organ culture and is likely responsible for changes in IOP observed in 3,7 dithia PGE1-treated monkey eyes.

Keywords: outflow: trabecular meshwork • anterior chamber 
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