Pemafibrate prevents retinal dysfunction in a mouse model of unilateral common carotid artery occlusion

Deokho Lee, Yohei Tomita, Heonuk Jeong, Yukihiro Miwa, Kazuo Tsubota, Kazuno Negishi, Toshihide Kurihara

Research output: Contribution to journalArticlepeer-review

Abstract

Cardiovascular diseases lead to retinal ischemia, one of the leading causes of blindness. Retinal ischemia triggers pathological retinal glial responses and functional deficits. Therefore, maintaining retinal neuronal activities and modulating pathological gliosis may prevent loss of vi-sion. Previously, pemafibrate, a selective peroxisome proliferator-activated receptor alpha modu-lator, was nominated as a promising drug in retinal ischemia. However, a protective role of pem-afibrate remains untouched in cardiovascular diseases-mediated retinal ischemia. Therefore, we aimed to unravel systemic and retinal alterations by treating pemafibrate in a new murine model of retinal ischemia caused by cardiovascular diseases. Adult C57BL/6 mice were orally administered pemafibrate (0.5 mg/kg) for 4 days, followed by unilateral common carotid artery occlusion (UCCAO). After UCCAO, pemafibrate was continuously supplied to mice until the end of exper-iments. Retinal function (a-and b-waves and the oscillatory potentials) was measured using elec-troretinography on day 5 and 12 after UCCAO. Moreover, the retina, liver, and serum were sub-jected to qPCR, immunohistochemistry, or ELISA analysis. We found that pemafibrate enhanced liver function, elevated serum levels of fibroblast growth factor 21 (FGF21), one of the neuropro-tective molecules in the eye, and protected against UCCAO-induced retinal dysfunction, observed with modulation of retinal gliosis and preservation of oscillatory potentials. Our current data suggest a promising pemafibrate therapy for the suppression of retinal dysfunction in cardiovascular diseases.

Original languageEnglish
Article number9408
JournalInternational journal of molecular sciences
Volume22
Issue number17
DOIs
Publication statusPublished - 2021 Sep 1

Keywords

  • Common carotid artery occlusion
  • Electroretinography
  • Fibroblast growth factor 21
  • Pemafibrate
  • Peroxisome proliferator-activated receptor alpha
  • Retinal ischemia

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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