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

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 re...

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Main Authors: Yohei Tomita, Deokho Lee, Yukihiro Miwa, Xiaoyan Jiang, Masayuki Ohta, Kazuo Tsubota, Toshihide Kurihara
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/17/6243
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author Yohei Tomita
Deokho Lee
Yukihiro Miwa
Xiaoyan Jiang
Masayuki Ohta
Kazuo Tsubota
Toshihide Kurihara
author_facet Yohei Tomita
Deokho Lee
Yukihiro Miwa
Xiaoyan Jiang
Masayuki Ohta
Kazuo Tsubota
Toshihide Kurihara
author_sort Yohei Tomita
collection DOAJ
description 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.
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spelling doaj.art-6541edededfa46c7a3293777e68ec5c52023-11-20T11:45:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012117624310.3390/ijms21176243Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic RetinopathyYohei Tomita0Deokho Lee1Yukihiro Miwa2Xiaoyan Jiang3Masayuki Ohta4Kazuo Tsubota5Toshihide Kurihara6Laboratory of Photobiology, Keio University School of Medicine, Tokyo 160-8582, JapanLaboratory of Photobiology, Keio University School of Medicine, Tokyo 160-8582, JapanLaboratory of Photobiology, Keio University School of Medicine, Tokyo 160-8582, JapanLaboratory of Photobiology, Keio University School of Medicine, Tokyo 160-8582, JapanKowa Company, Ltd., Tokyo 103-8433, JapanDepartment of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, JapanLaboratory of Photobiology, Keio University School of Medicine, Tokyo 160-8582, JapanDiabetic 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.https://www.mdpi.com/1422-0067/21/17/6243diabetes retinopathy (DR)electroretinography (ERG)fibroblast growth factor21 (FGF21)pemafibratestreptozotocin (STZ)synaptophysin
spellingShingle Yohei Tomita
Deokho Lee
Yukihiro Miwa
Xiaoyan Jiang
Masayuki Ohta
Kazuo Tsubota
Toshihide Kurihara
Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic Retinopathy
International Journal of Molecular Sciences
diabetes retinopathy (DR)
electroretinography (ERG)
fibroblast growth factor21 (FGF21)
pemafibrate
streptozotocin (STZ)
synaptophysin
title Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic Retinopathy
title_full Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic Retinopathy
title_fullStr Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic Retinopathy
title_full_unstemmed Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic Retinopathy
title_short Pemafibrate Protects Against Retinal Dysfunction in a Murine Model of Diabetic Retinopathy
title_sort pemafibrate protects against retinal dysfunction in a murine model of diabetic retinopathy
topic diabetes retinopathy (DR)
electroretinography (ERG)
fibroblast growth factor21 (FGF21)
pemafibrate
streptozotocin (STZ)
synaptophysin
url https://www.mdpi.com/1422-0067/21/17/6243
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