Prostaglandin F2α Receptor Modulation Affects Eye Development in Guinea Pigs.

Abstract

Retinal arachidonic acid (ARA) levels in form-deprived eyes decline in guinea pigs. As prostaglandin F2α (PGF2α) is an ARA metabolite and endogenous agonist of prostaglandin F receptor (FP), we have been suggested that down-regulation of PGF2α-FP receptor signalling pathway contributes to myopia onset. To test this hypothesis, this study determines whether: (i) retinal PGF2α levels decline during the development of form deprivation myopia (FDM) in guinea pigs; (ii) FP receptor agonism and antagonism alter emmetropization and myopia development. Pigmented guinea pigs were randomly assigned to normal vision and form-deprived groups. Ultraperformance liquid chromatography coupled with a mass spectrometer (UPLC-MS) measured retinal PGF2α levels 2weeks after form deprivation (FD). The selective FP agonist, latanoprost acid (LAT) and its corresponding antagonist, AL8810, were peribulbarly injected into each group. An eccentric infrared photorefractor (EIR) monitored refraction. A-scan ultrasonography measured axial elongation (AL) and vitreous chamber depth (VCD). Tonometry measured the intraocular pressure (IOP). Retinal PGF2α levels declined in form-deprived eyes compared to those in normal eyes. Neither LAT nor AL8810 affected IOP with or without FD. On the other hand, after 4weeks of daily 0.5μg AL8810 treatment, a myopia of -1.99±0.34dioptre (D) developed, but LAT had no effect on emmetropization in a normal visual environment. Nevertheless, daily 30μg LAT treatment for 4weeks inhibited FDM development by 41% (vehicle control: -8.39±0.45D; LAT: -4.95±0.39D; two-way anova with repeated measures, p<0.05). Down-regulation of PGF2α-FP receptor signalling pathway may contribute to myopia onset as retinal PGF2α declined in myopic eyes and antagonism of FP receptor by AL8810 induced a myopic shift in normal vision environment. Meanwhile, up-regulation of this pathway by LAT inhibited FDM development. However, the mechanism underlying LAT-induced FDM inhibition needs further clarification. This uncertainty exists because its inhibition of FDM suggests that LAT strengthens the scleral framework which reduces axial elongation. On the other hand, its IOP-lowering effect is attributed to thinning and weakening the scleral framework in glaucoma treatment.