Retinal degeneration induced in a mouse model of ischemia–reperfusion injury and its management by pemafibrate treatment

Deokho Lee, Ayaka Nakai, Yukihiro Miwa, Yohei Tomita, Hiromitsu Kunimi, Junhan Chen, Shin Ichi Ikeda, Kazuo Tsubota, Kazuno Negishi, Toshihide Kurihara

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Retinal ischemia–reperfusion (I/R) injury is a common cause of visual impairment. To date, no effective treatment is available for retinal I/R injury. In addition, the precise pathological mechanisms still need to be established. Recently, pemafibrate, a peroxisome proliferator-activated receptor α (PPARα) modulator, was shown to be a promising drug for retinal ischemia. However, the role of pemafibrate in preventing retinal I/R injury has not been documented. Here, we investigated how retinal degeneration occurs in a mouse model of retinal I/R injury by elevation of intraocular pressure and examined whether pemafibrate could be beneficial against retinal degeneration. Adult mice were orally administered pemafibrate (0.5 mg/kg/day) for 4 days, followed by retinal I/R injury. The mice were continuously administered pemafibrate once every day until the end of the experiments. Retinal functional changes were measured using electroretinography. Retina, liver, and serum samples were used for western blotting, quantitative PCR, immunohistochemistry, or enzyme linked immunosorbent assay. Retinal degeneration induced by retinal inflammation was prevented by pemafibrate administration. Pemafibrate administration increased the hepatic PPARα target gene expression and serum levels of fibroblast growth factor 21, a neuroprotective molecule in the eye. The expression of hypoxia-response and pro-and anti-apoptotic/inflammatory genes increased in the retina following retinal I/R injury; however, these changes were modulated by pemafibrate administration. In conclusion, pemafibrate is a promising preventive drug for ischemic retinopathies.

Original languageEnglish
Article numbere22497
JournalFASEB Journal
Volume36
Issue number9
DOIs
Publication statusPublished - 2022 Sep

Keywords

  • fibroblast growth factor 21 (FGF21)
  • inflammation
  • neuroprotection
  • pemafibrate
  • peroxisome proliferator-activated receptor α (PPARα)
  • retinal ischemia and degeneration

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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