Fenofibrate protects against retinal dysfunction in a murine model of common carotid artery occlusion-induced ocular ischemia

Deokho Lee, Yohei Tomita, Yukihiro Miwa, Heonuk Jeong, Kiwako Mori, Kazuo Tsubota, Toshihide Kurihara

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Ocular ischemia is a common cause of blindness and plays a detrimental role in various diseases such as diabetic retinopathy, occlusion of central retinal arteries, and ocular ischemic syndrome. Abnormalities of neuronal activities in the eye occur under ocular ischemic conditions. Therefore, protecting their activities may prevent vision loss. Previously, peroxisome proliferator-activated receptor alpha (PPARα) agonists were suggested as promising drugs in ocular ischemia. However, the potential therapeutic roles of PPARα agonists in ocular ischemia are still unknown. Thus, we attempted to unravel systemic and ocular changes by treatment of fenofibrate, a well-known PPARα agonist, in a new murine model of ocular ischemia. Adult mice were orally administered fenofibrate (60 mg/kg) for 4 days once a day, followed by induction of ocular ischemia by unilateral common carotid artery occlusion (UCCAO). After UCCAO, fenofibrate was continuously supplied to mice once every 2 days during the experiment period. Electroretinography was performed to measure retinal functional changes. Furthermore, samples from the retina, liver, and blood were subjected to qPCR, Western blot, or ELISA analysis. We found that fenofibrate boosted liver function, increased serum levels of fibroblast growth factor 21 (FGF21), one of the neuroprotective molecules in the central nervous system, and protected against UCCAO-induced retinal dysfunction. Our current data suggest a promising fenofibrate therapy in ischemic retinopathies.

Original languageEnglish
Article number223
JournalPharmaceuticals
Volume14
Issue number3
DOIs
Publication statusPublished - 2021 Mar

Keywords

  • Common carotid artery
  • Electroretinography
  • Fenofibrate
  • Fibroblast growth factor 21
  • Peroxisome proliferator-activated receptor alpha

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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