May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Effect of Prostaglandin Analogues on IOP in Prostanoid EP1 and EP3 Receptor Deficient Mice
Author Affiliations & Notes
  • T. Ota
    Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  • M. Aihara
    Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  • S. Narumiya
    Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto, Japan
  • M. Araie
    Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan
  • Footnotes
    Commercial Relationships  T. Ota, None; M. Aihara, None; S. Narumiya, None; M. Araie, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 3775. doi:
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      T. Ota, M. Aihara, S. Narumiya, M. Araie; Effect of Prostaglandin Analogues on IOP in Prostanoid EP1 and EP3 Receptor Deficient Mice . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3775.

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

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Abstract

Abstract: : Purpose: To clarify whether prostanoid EP1 and EP3 receptors are concerned with the mechanism of IOP and IOP–lowering effect of prostaglandin analogues (PGs). Methods: EP1 receptor deficient (EP1–/–), EP3 receptor deficient (EP3–/–) and wild type (EP1+/+ and EP3+/+) mice aged more than 8 weeks were used. Animals were acclimatized under the 12–hour light–dark cycle (6:00 on 18:00 off) for at least 2 weeks before experiments. IOP was measured by a microneedle method. Three micro litters of 0.005% latanoprost (LAT), 0.004% travoprost (TRA), 0.03% bimatoprost (BIM), 0.12% unoprostone (UNO) or 0.0015% tafluprost (TAF) were topically applied once into one of two eyes in a blind manner at 18:00. The fellow eye was served as non–treated control. The IOP–lowering effect of each drug at 3 hours after the administration was calculated as the difference in IOP and reduction in IOP from the IOP of the not treated fellow eye. Results: The baseline IOP of EP1–/–, EP3–/–, EP1+/+ and EP3+/+ mouse were not significantly different among genotypes. The baseline IOP was higher in nighttime than in daytime, and the IOP–lowering effect of LAT was greater in nighttime than daytime. At 3 hours after the administration, IOP reduction by LAT, TRA, BIM, UNO, and TAF were 18.6+/–1.6 (MEAN+/–SEM), 25.8+/–1.7, 18.1+/–1.6, 11.3+/–1.5 and 26.3+/–0.8% (N=10 or 11) in EP1–/– mice, 15.0+/–1.9, 15.4+/–1.5, 13.1+/–2.1, 11.7+/–1.3 and 17.4+/–1.8% (N=11 or 12) in EP3–/– mice, 22.3+/–1.4, 25.8+/–2.0, 19.5+/–2.1, 12.7+/–2.4 and 25.5+/–4.3% (N=5–7) in EP1+/+ mice, and 23.2+/–1.1, 26.1+/–1.2, 19.8+/–1.5, 13.7+/–1.8 and 25.8+/–2.6% (N=8–11) in EP3+/+ mice, respectively. There was no significant difference in IOP–lowering effect between EP1+/+ and EP1–/– mice treated with each drug. On the other hand, in EP3–/– mice, the IOP–lowering effects of PGs, except for UNO were found to be weak (P<0.05). Conclusions: EP3 receptor may play a role in IOP–lowering effect of LAT, TRA, BIM and TAF.

Keywords: pharmacology • intraocular pressure • drug toxicity/drug effects 
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