A selective PPARα modulator has preventive effects in murine models of retinopathy

Abstract

Purpose : Large-scale clinical trials such as FIELD and ACCORD have shown that administration of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, suppresses the progression of diabetic retinopathy. In this study, we examine therapeutic effects of K877 (pemafibrate), a novel selective PPARα modulator, against pathogenesis in the retina utilizing murine models of retinopathy.

Methods : Oxygen-induced retinopathy (OIR) was induced in C57BL/6J mice by exposure to 85% oxygen from postnatal day 8 (P8) for 72 hours. Pemafibrate (P group), fenofibrate (F group) and vehicle (V group) were subcutaneously injected from P12 to P16 daily. At P17, Vaso-obliteration and neovascular tufts formation were evaluated on the wholemount retinae with isolectin B4 staining. Streptozotocin (STZ)-induced diabetic mouse model were also examined. Mice were fed chow containing pemafibrate (p group), fenofibrate (f group) or vehicle (v group) for three months after the high glycaemia induction. Non-diabetic mice with vehicle-contained chow were also prepared (NDM group). For the STZ model, the thickness of the retinal inner layer using optical coherence tomography (OCT) and visual function using electroretinogram (ERG) were evaluated.

Results : In the OIR model, Neovascular tufts were significantly decreased in the P group compared to the V group (P=0.02), while there were no significant differences in the F group in comparison with V group. There were no significant differences in vaso-obliteratoin with each group. In the STZ model, ganglion cell complex evaluated by OCT was significantly thinner in the p, f and v group compared to NDM group (P<0.01), whereas there were no significant differences between other groups. The scotopic mixed flash ERG showed that the amplitude of the b-wave and the oscillatory potentials wave were significantly higher in the p group than in the v group (P<0.02, respectively)

Conclusions : Pemafibrate may have therapeutic effects to prevent pathological neovascularization and neurodegeneration in retinal diseases such as diabetic retinopathy.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.