April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Comparison of the Effects of an EP2, EP4 and EP2/4 Agonist on Aqueous Humor Dynamics in Monkeys
Author Affiliations & Notes
  • C. B. Toris
    Ophthalmology, Univ of Nebraska Medical Ctr, Omaha, Nebraska
  • S. Fan
    Ophthalmology, Univ of Nebraska Medical Ctr, Omaha, Nebraska
  • L. S. Stapp
    Ophthalmology, Univ of Nebraska Medical Ctr, Omaha, Nebraska
  • T. L. Rudebush
    Ophthalmology, Univ of Nebraska Medical Ctr, Omaha, Nebraska
  • G. Prasanna
    Pfizer, La Jolla, California
  • S. Anderson
    Pfizer, La Jolla, California
  • A. Krauss
    Pfizer, La Jolla, California
  • Footnotes
    Commercial Relationships  C.B. Toris, Pfizer, F; S. Fan, None; L.S. Stapp, None; T.L. Rudebush, None; G. Prasanna, Pfizer, E; S. Anderson, Pfizer, E; A. Krauss, Pfizer, E.
  • Footnotes
    Support  Pfizer; Research to Prevent Blindness
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2007. doi:
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    • Get Citation

      C. B. Toris, S. Fan, L. S. Stapp, T. L. Rudebush, G. Prasanna, S. Anderson, A. Krauss; Comparison of the Effects of an EP2, EP4 and EP2/4 Agonist on Aqueous Humor Dynamics in Monkeys. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2007.

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Abstract
 
Purpose:
 

The purpose of this study was to determine the effects of an EP2, EP4 and a mixed EP2/4 agonist on intraocular pressure (IOP) and aqueous humor dynamics in monkeys.

 
Methods:
 

Three masked, crossover experiments were performed in 12 to 14 female cynomolgus monkeys with unilateral laser-induced glaucoma. Seated intraocular pressures were measured in conscious animals by pneumatonometry at 9AM on baseline day (IOP1). Eyes were dosed once-daily for three days with agonists of EP2 (0.01%), EP4 (0.00025%) or EP2-and-4 (0.0005%) receptors, or vehicle. Measurements on day 4 of dosing were made in ketamine sedated animals. These included IOPs by pneumatonometry at 9AM (IOP2) and noon (IOP3), aqueous flow (Fa, µl/min) by fluorophotometry, outflow facility (µl/min/mmHg) by fluorophotometry (Cfl) and by 2-minute tonography (Cton), and uveoscleral outflow (Fufl or Futon, µl/min) by mathematical calculation.

 
Results:
 

Results are summarized in Table. Values are Means±SD. Drug treatments and corresponding vehicle treatments were compared by two-tailed paired t-tests (p).  

 
Conclusions:
 

The EP2, EP4 and mixed EP2/4 agonists in this study reduced IOP by increasing uveoscleral outflow. The two determinations of uveoscleral outflow (Fufl and Futon) showed increases of at least 1.2-fold with drug treatment compared to vehicle treatment, however these findings were not always statistically significant. Unlike another study of a different EP4 agonist, outflow facility was unchanged by the EP4 agonist in the current study.

 
Keywords: aqueous • intraocular pressure 
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