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

doi:10.7717/peerj.14611

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

PeerJ. 2023 Jan 10:11:e14611. doi: 10.7717/peerj.14611. eCollection 2023.

Authors

Deokho Lee^{1

2}, Ayaka Nakai^{1

2

3}, Yukihiro Miwa^{1

2

4}, Kazuno Negishi², Yohei Tomita^{1

2}, Toshihide Kurihara^{1

2}

Affiliations

¹ Laboratory of Photobiology, Keio University School of Medicine, Tokyo, Japan.
² Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
³ Ophthalmology, Nihon University School of Medicine, Tokyo, Japan.
⁴ Aichi Animal Eye Clinics, Aichi, Japan.

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.

Keywords: Choroid; Eye; Neovascularization; Pemafibrate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Choroidal Neovascularization* / drug therapy
Disease Models, Animal
Macular Degeneration* / drug therapy
Male
Mice
Mice, Inbred C57BL
PPAR alpha / therapeutic use
Vascular Endothelial Growth Factor A / metabolism

Substances

(R)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid
PPAR alpha
Vascular Endothelial Growth Factor A

Grants and funding

This work was supported by Grants-in-Aid for Scientific Research (KAKENHI, number 15 K10881, and 18 K09424) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to Toshihide Kurihara and JST SPRING (number JPMJSP2123) to Deokho Lee. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.