Neuroprotective Effect of Oral Pemafibrate with Suppression of p-ULK1 Elevation in a Rat Ocular Hypertension-Induced Glaucoma Model.

PURPOSE: Pemafibrate was developed as a selective modulator of peroxisome proliferator-activated receptor alpha and is used as a treatment for hyperlipidemia. Although recent studies have shown a variety of functions in vivo, its effects on optic nerve axons remain unclear. The purpose of this study was to investigate the effects of oral administration of pemafibrate in a rat model of ocular hypertension glaucoma and to address its molecular mechanisms. METHODS: Laser irradiation was used to create the rat model of ocular hypertension glaucoma. Pemafibrate was administered daily, and retinal nerve fibers were quantified, and optic nerve axon numbers were quantified after 3 weeks. Western blotting was performed to measure the expression of p-ULK1 Ser757. RESULTS: Pemafibrate significantly inhibited axonal loss in the hypertensive glaucoma model, as well as loss of retinal nerve fibers in the peripheral area. Western blot analysis revealed an increase in p-ULK1 Ser757 in the retina of the hypertensive glaucoma model, which was significantly suppressed in the pemafibrate-treated group. CONCLUSIONS: These results suggest that pemafibrate may have neuroprotective effects associated with suppression of OHT-induced p-ULK1 Ser757 elevation. Because autophagic flux was not directly measured, the present findings suggest a possible modulatory role in autophagy-related signaling rather than demonstrating restoration of autophagy function.