Opposing Effects of PPARα Agonism and Antagonism on Refractive Development and Form Deprivation Myopia in Guinea Pigs

作者：Miaozhen Pan, Shiming Jiao, Peter S. Reinach, Jiaofeng Yan, Yanan Yang, Qihang Li, Nethrajeith Srinivasalu, Jia Qu, Xiangtian Zhou · 发表于：Investigative Ophthalmology & Visual Science · 年份：2018 · DOI：10.1167/iovs.17-22297 · 被引用次数：20 · 研究领域：Ophthalmology and Visual Impairment Studies、Glaucoma and retinal disorders、Corneal surgery and disorders

Purpose: To determine if drug-induced peroxisome proliferator-activated receptor α (PPARα) signal pathway modulation affects refractive development and myopia in guinea pigs. Methods: Pigmented guinea pigs were randomly divided into normal vision (unoccluded) and form deprivation myopia (FDM) groups. Each group received daily peribulbar injections of either a vehicle or (1) PPARα agonist, GW7647, clofibrate, or bezafibrate or (2) PPARα antagonist, GW6471, for 4 weeks. Baseline and posttreatment refraction and ocular biometric parameters were measured. Immunofluorescent staining of PPARα and two of its downstream readouts, cytosolic malic enzyme 1 (ME1) and apolipoproteinA II (apoA-II), was undertaken in selected scleral sections. Western blot analysis determined collagen type I expression levels. Results: GW6471 induced a myopic shift in unoccluded eyes, but had no effect on form-deprived eyes. Conversely, GW7647 inhibited FDM progression without altering unoccluded eyes. Bezafibrate and clofibrate had effects on refraction similar to those of GW7647 in unoccluded and form-deprived eyes. GW6471 downregulated collagen type I expression in unoccluded eyes whereas bezafibrate inhibited collagen type I decreases in form-deprived eyes. GW6471 also reduced the density of ME1- and apoA-II-stained cells in unoccluded eyes whereas bezafibrate increased apoA-II-positive cell numbers in form-deprived eyes. Conclusions: As GW7647 and GW6471 had opposing effects on myopia development, PPA...