Effect of FP receptor and endogenous PG production against transient ocular hypertension induced by PGE₂ and PGF_2α in mouse eyes.

Abstract

Purpose: We previously reported that PGE₂ and PGF_2α induced transient ocular hypertension in mouse eyes. However, the mechanism has not been clarified. In this study, we investigated the possible implication of FP receptor and endogenous PGs for transient ocular hypertension by PGE₂ and PGF_2α.

Methods: Intraocular pressure (IOP) was measured at day time using micro needle method in mouse eyes. A single drop with 3 μL aliquots of saline or 0.1% nepafenac solution (NEP), one of the NSAIDs, were topically applied into randomly selected one of two eyes in C57BL6 (WT), FP, EP1, EP2 and EP3 knock-out (KO) mice. After 30min, 0.1%PGE₂ methyl ester (=PGE₂) or PGF_2α methyl ester (=PGF_2α) were additionally dropped, and IOP was measured 60min later.<br /> IOP change was evaluated by the difference between IOP of the treated eye (IOPtx) and that of the contralateral control eye (IOPc) and the percentage of IOP inrease was calculated by 100x(IOPtx - IOPc)/IOPc in each mouse.

Results: IOP increase by PGE₂ in WT, and FP, EP1, EP2 and EP3KO mice were 7.5±5.3, 27.9±11.6, 7.9±5.6, 8.7±5.5 and 6.2±6.0%, respectively. Conversely, those by NEP+PGE₂ showed 4.8±6.6, 5.6±4.5, 10.5±8.3, 8.0±8.7 and 11.7±6.4%, respectively. Further, IOP increase by PGF_2α were 8.9±6.6, 16.9±5.1, 6.4±5.5, 4.6±9.1 and 1.4±7.6%, respectively. In contrast, NEP＋PGF_2α showed 5.0±7.8, 2.5±3.0, 6.6±6.3, 5.5±5.2 and 3.5±2.1%, respectively. Transient ocular hypertension was induced in all types of mice by PGE₂ and PGF_2α, but was significantly enhanced in FPKO mouse compared to the other mice. (p<0.01) Moreover, the enhancement of ocular hypertension was significantly suppressed by NEP treatment. (p<0.01)

Conclusions: It became clear that transient ocular hypertension induced by PGE₂ and PGF_2α in mouse eyes might involve FP receptor and endogenous PG production.