Effect of a Single Dose of Latanoprost on Intraocular Pressure in FP Receptor Knockout Mice

Abstract

Abstract: : Purpose: The active metabolite of the prostaglandin analogue latanoprost is thought to mediate its ocular hypotensive effect through activation of the FP receptor. However, possible non–FP receptor effects on IOP have been proposed. The aim of this study was to determine the effect of latanoprost on IOP in mice lacking the FP receptor. Methods: Mouse genotype was determined by PCR of tissue obtained from tail biopsies. A single 4 μl drop of latanoprost (0.01%) was applied to the right eye and IOP was measured after two–hours in both the treated eye and untreated fellow eye. The investigator was blinded to mouse genotype at the time of IOP measurement. IOP was measured by intracameral insertion of a microneedle attached to a pressure transducer. Results: 16–heterozygote and 10–homozygote mice were identified by PCR. Mean baseline IOP was similar in the homozygous knockout mice, in the heterozygous mice and in the background strain, wildtype C57/Black6 mice as well as in Swiss White wild–type mice which both have normal FP receptor expression. Latanoprost had no effect on IOP in homozygous FP knockouts. However, a significant reduction in IOP was observed in the treated eye of the heterozygote and wild–type mice. Change in IOP after a single treatment of latanoprost 

Conclusion: These data indicate that FP receptor expression is necessary for the ocular hypotensive effect of latanoprost.

Keywords: pharmacology • drug toxicity/drug effects • transgenics/knock–outs