Pemafibrate prevents choroidal neovascularization in a mouse model of neovascular age-related macular degeneration

Deokho Lee, Ayaka Nakai, Yukihiro Miwa, Kazuno Negishi, Yohei Tomita, Toshihide Kurihara

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Pathological choroidal neovascularization (CNV) is one of the major causes of visual impairment in neovascular age-related macular degeneration (AMD). CNV has been suppressed by using anti-vascular endothelial growth factor (VEGF) antibodies. However, some clinical cases have demonstrated the failure of anti-VEGF therapies. Furthermore, anti-VEGF agents might induce the development of ocular atrophy. Recently, peroxisome proliferator-activated receptor alpha (PPARα) activation using pemafibrate treatment was suggested as one of the promising therapeutic targets in the prevention of ocular ischemia. However, the preventive role of pemafibrate remains unclear in CNV. We aimed to examine the preventive role of pemafibrate on laser-induced pathological CNV. Methods. Adult male C57BL/6 mice were orally supplied pemafibrate (0.5 mg/kg) for four days, followed by laser irradiation. Then, pemafibrate was consecutively given to mice with the same condition. CNV was visualized with isolectin-IB4. The eye (retina and/or retinal pigment epithelium [RPE]-choroid), liver, and serum were used for biomolecular analyses. Results. We found that pemafibrate administration suppressed CNV volumes. Pemafibrate administration activated PPARα downstream genes in the liver and eye (especially, RPE-choroid). Furthermore, pemafibrate administration elevated serum fibroblast growth factor 21 levels and reduced serum levels of triglycerides. Conclusions. Our data suggest a promising pemafibrate therapy for suppressing CNV in AMD.

Original languageEnglish
Article numbere14611
JournalPeerJ
Volume11
DOIs
Publication statusPublished - 2023 Jan

Keywords

  • Choroid
  • Eye
  • Neovascularization
  • Pemafibrate

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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