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Reiko Yamagishi, Kazufumi Nagai, Shinsaku Yamane, Makoto Aihara; IOP lowing effect of prostanoid FP and EP3 receptor dual agonist on mouse eyes. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5630.
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© ARVO (1962-2015); The Authors (2016-present)
We previously reported that the IOP-lowering effect by the stimulation of FP receptor involved EP3 receptor stimulation through the EP3 receptor. In this study, we made a comparison closely between FP receptor and FP/EP3 receptor dual agonist. Moreover, we examined the effect of FP/EP3 receptor dual agonist on IOP reduction in order to confirm the involvement of EP3 receptor. For elucidation of the mechanism of IOP reduction, we performed similar experiments using C57BL6 mice (WT) , FP receptor deficient mice (FPKO) , EP3 receptor deficient mice (EP3KO) and WT pre-treated with NSAIDs (WT + NSAIDs).
A single drop with 3 μL aliquots of 0.003% ONO-AG-241 (=ONO, FP/EP3 dual agonist), or 0.005% latanoprost (=LAT, FP agonist), were topically applied into randomly selected one of two eyes in ddY mouse. We measured IOP over time with a micro needle method. IOP reduction was evaluated by the difference between IOP of the treated eye and that of the contralateral control eye. Further, we measured IOP in WT, FPKO, EP3KO, and WT+NSAIDs at 2 and 8 hours after instillation.
Significant IOP reductions were observed at 2 (17.1±2.1%; p< 0.01) and 4 (13.0±2.9%; p< 0.01) hours after LAT instillation, but not at 6 and 8 hours. ONO showed similar but prolonged IOP lowering effect at 2 (16.1±4.0%; p< 0.01), 4 (16.6±2.0%; p< 0.01), 6 (13.7±2.2%; p< 0.01) and 8 (10.5±2.1%; p< 0.01) hours after instillation. Two hours after instillation of LAT, IOP reduction in WT, FPKO, EP3KO and WT+NSAIDs were 15.0±0.7%, 1.5±1.0%, 11.2±0.6%, and 12.9±0.6%, respectively. The IOP reduction induced by LAT in FPKO was significantly decreased compared to WT. (p<0.05) IOP reduction by ONO in WT, FPKO, EP3KO and WT+NSAIDs were 15.4±0.7%, 9.4±0.9%, 11.4±1.0%, and 11.2±0.6%, respectively. The IOP reduction induced by ONO showed no difference among all types of mice. Eight hours after instillation, LAT induced no IOP reduction in all types of mice. However, ONO still reduced IOP in WT, FPKO, EP3KO and WT+NSAIDs, which were 11.6±0.7%, 9.0±0.7%, 4.1±0.5%, and 5.6±0.7%, respectively. The IOP reduction at 8 hours after ONO instillation in EP3KO mice was significantly decreased in WT mice. (p<0.05)
FP/EP3 receptor dual agonist induced significant and prolonged IOP reduction compared to latanoprost in mouse eyes. IOP-lowing effect of FP/EP3 receptor dual agonist may involve endogenous PG production and EP3 receptor stimulation.
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