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The IOP-lowering effects and mechanism of action of tafluprost in prostanoid receptor-deficient mice
  1. Takashi Ota1,
  2. Makoto Aihara1,
  3. Tadashiro Saeki1,
  4. Shuh Narumiya2,
  5. Makoto Araie1
  1. 1Department of Ophthalmology, University of Tokyo School of Medicine, Hongo Bunkyo-ku, Tokyo, Japan
  2. 2Department of Pharmacology, Kyoto University Faculty of Medicine, Japan
  1. Correspondence to: Dr M Aihara Department of Ophthalmology, University of Tokyo School of Medicine, 7-3-1 Hongo Bunkyo-ku Tokyo 113-8655, Japan; aihara-tky{at}umin.ac,jp

Abstract

Aim: To clarify the intraocular pressure (IOP)-lowering profile of tafluprost, a newly synthesised prostaglandin F analogue, in mice.

Methods: C57BL/6J, and EP1, EP2, EP3 and postaglandin F (FP) receptor-deficient wild-type (WT), EP1KO, EP2KO, EP3KO and FPKO, respectively mice were bred and acclimatised under a 12-h (6:00–18:00) light–dark cycle. To evaluate effects of tafluprost (0.002%) on IOP at night, a single 3 µl drop of tafluprost solution was applied topically at 18:00 once into one eye in each mouse. IOP was measured 3 h after the application with a microneedle method. To clarify whether endogenous prostaglandin is concerned with the tafluprost-induced IOP reduction, we applied 0.1% diclofenac Na, a cyclo-oxygenase inhibitor or PBS 30 min before the application of tafluprost in WT and EP3KO mice and measured IOP 3 h after the tafluprost application. We also determined whether animals responded predictably to 0.1% bunazosin HCl, a drug known to increase uveoscleral outflow.

Results: 3 h after the application of 0.0015% tafluprost, mean (SEM) IOP reductions were 25.8 (2.1)% 26.3 (0.8)% 24.2 (1.4)% 16.5 (1.7)% and −0.9 (1.5)% in WT, EP1KO, EP2KO, EP3KO and FPKO mice, respectively. IOP reductions in EP3KO and FPKO mice were significantly smaller than in WT mice. Pretreatment with diclofenac Na significantly attenuated the IOP lowering effect of tafluprost in WT mice but not in EP3KO mice. Bunazosin HCl lowered IOP significantly in all genotypes by the same amount.

Conclusion: We conclude that tafluprost lowers IOP through the prostanoid FP receptor. A part of ocular hypotensive effect of tafluprost is attributed to FP receptor-mediated prostaglandin production acting through the prostanoid EP3 receptor.

  • IOP, intraocular pressure
  • FP, prostaglandin F
  • PG, prostaglandin
  • PBS, phosphate-buffered saline
  • WT, wild-type

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Footnotes

  • Published online first 22 November 2006

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