HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Crowston, J. G. Articles by Weinreb, R. N. Search for Related Content PubMed PubMed Citation Articles by Crowston, J. G. Articles by Weinreb, R. N.

Effect of Bimatoprost on Intraocular Pressure in Prostaglandin FP Receptor Knockout Mice

¹From the Hamilton Glaucoma Center and Department of Ophthalmology, University of California San Diego, La Jolla, California; and ²Allergan USA, Irvine, California.

PURPOSE. To determine the effect of bimatoprost on intraocular pressure in the prostaglandin FP receptor knockout mouse.

METHODS. The IOP response to a single 1.2-µg (4 µL) dose of bimatoprost was measured in the treated and untreated fellow eyes of homozygote (FP^+/+, n = 9) and heterozygote (FP^±, n = 10) FP-knockout mice, as well as in wild-type C57BL/6 mice (FP^+/+, n = 20). Serial IOP measurements were also performed after topical bimatoprost in a separate generation of homozygous FP-knockout mice and wild-type littermate control animals (n = 4 per group). Aqueous humor protein concentrations were measured to establish the state of the blood–aqueous barrier. Tissue, aqueous humor and vitreous concentrations of bimatoprost, latanoprost, and their C-1 free acids were determined by liquid chromatography and tandem mass spectrometry.

RESULTS. A significant reduction in IOP was observed in the bimatoprost-treated eye of wild-type mice at 2 hours, with a mean difference and 95% confidence interval (CI) of the difference in means of –1.33 mm Hg (–0.81 to –1.84). Bimatoprost did not lead to a significant reduction in IOP in either the heterozygous knockout –0.36 mm Hg (–0.82 to +0.09) or homozygous FP-knockout mice 0.25 mm Hg (–0.38 to +0.89). The lack of an IOP response in the FP-knockout mice was not a consequence of blood–aqueous barrier breakdown, as there was no significant difference in aqueous humor protein concentration between treated and fellow eyes. Tissue and aqueous humor concentrations of bimatoprost, latanoprost, and their C-1 free acids indicate that latanoprost, but not bimatoprost, is hydrolyzed in the mouse eye after topical administration.

CONCLUSIONS. An intact FP receptor gene is critical to the IOP response to bimatoprost in the mouse eye.

This article has been cited by other articles:

				C B Camras, N A Sharif, M B Wax, and J Stjernschantz Bimatoprost, the prodrug of a prostaglandin analogue Br. J. Ophthalmol., June 1, 2008; 92(6): 862 - 863. [Full Text] [PDF]

				L B Cantor Author's reply Br. J. Ophthalmol., June 1, 2008; 92(6): 863 - 864. [Full Text] [PDF]

				J. G. Crowston, C. A. Morris, J. D. Lindsey, and R. N. Weinreb Prostaglandin FP Receptors Do Not Contribute to 24-hour Intraocular Pressure Variation in Mice Invest. Ophthalmol. Vis. Sci., May 1, 2007; 48(5): 2095 - 2098. [Abstract] [Full Text] [PDF]

				T. Ota, M. Aihara, T. Saeki, S. Narumiya, and M. Araie The Effects of Prostaglandin Analogues on Prostanoid EP1, EP2, and EP3 Receptor-Deficient Mice. Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3395 - 3399. [Abstract] [Full Text] [PDF]