Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic Retinopathy.

Yohei Tomita,Masayuki Ohta,Yukihiro Miwa,Toshihide Kurihara,Kazuo Tsubota,Deokho Lee,Xiaoyan Jiang

doi:10.3390/ijms21176243

Abstract

Diabetic retinopathy (DR) is one of the leading causes of blindness globally. Retinal neuronal abnormalities occur in the early stage in DR. Therefore, maintaining retinal neuronal activity in DR may prevent vision loss. Previously, pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, was suggested as a promising drug in hypertriglyceridemia. However, the role of pemafibrate remains obscure in DR. Therefore, we aimed to unravel systemic and retinal changes by pemafibrate in diabetes. Adult mice were intraperitoneally injected with streptozotocin (STZ) to induce diabetes. After STZ injection, diet supplemented with pemafibrate was given to STZ-induced diabetic mice for 12 weeks. During the experiment period, body weight and blood glucose levels were examined. Electroretinography was performed to check the retinal neural function. After sacrifice, the retina, liver, and blood samples were subjected to molecular analyses. We found pemafibrate mildly improved blood glucose level as well as lipid metabolism, boosted liver function, increased serum fibroblast growth factor21 level, restored retinal functional deficits, and increased retinal synaptophysin protein expression in STZ-induced diabetic mice. Our present data suggest a promising pemafibrate therapy for the prevention of early DR by improving systemic metabolism and protecting retinal function.

Highlights

Diabetic retinopathy (DR) is a common metabolic complication of diabetes, which has a significant impact on the world’s health systems [1]
On week 4, blood glucose level was significantly reduced by pemafibrate administration in STZ-induced diabetic mice (Figure 1C)
Pemafibrate lowers triglyceride concentration in the body, of which a high level is considered as a risk factor for the development of cardiovascular diseases [38] and increases high-density lipoprotein cholesterol levels [37]. We reproduced this finding in STZ-induced diabetic mice: We found a decrease in triglyceride concentration and an increase in total cholesterol levels that may be inferred as an increase in high-density lipoprotein cholesterol levels by the administration of pemafibrate

Summary

Introduction

Diabetic retinopathy (DR) is a common metabolic complication of diabetes, which has a significant impact on the world’s health systems [1]. DR often causes vision loss in people of working age, despite increasing evidence of the effectiveness of regular screening and early treatment for DR [1]. Most of the current treatments for DR try to regulate vascular changes through the vascular endothelial growth factor (VEGF), by laser treatment, and anti-VEGF drugs [2]. Since anti-VEGF drugs can affect physiological roles of VEGF in the retina, it may affect the retinal and blood vessel homeostasis [2]. Innovative and comprehensive approaches are needed to reduce the risk of vision loss, including degeneration of the neural retina as well as that of normal blood vessels. Dysfunction of retinal electrophysiology occurs in advance of vascular abnormalities in DR [3]. Boosting retinal function may help to prevent DR progression

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