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

Area of Science:

• Ophthalmology
• Molecular Biology
• Pharmacology

Background:

• Pathological choroidal neovascularization (CNV) is a leading cause of vision loss in neovascular age-related macular degeneration (AMD).
• Current anti-vascular endothelial growth factor (VEGF) therapies for CNV have limitations, including treatment failure and potential induction of ocular atrophy.
• Peroxisome proliferator-activated receptor alpha (PPARα) activation is a potential therapeutic strategy for ocular ischemia, but its role in CNV is not well understood.

Purpose of the Study:

• To investigate the preventive effect of pemafibrate, a PPARα activator, on laser-induced pathological CNV in a mouse model.
• To evaluate the impact of pemafibrate on CNV volume and related molecular markers.

Main Methods:

• Adult male C57BL/6 mice were treated with pemafibrate (0.5 mg/kg) orally for four days before and after laser induction of CNV.
• CNV volume was assessed using isolectin-IB4 staining.
• Biomolecular analyses were performed on eye tissues (retina, RPE-choroid), liver, and serum.

Main Results:

• Pemafibrate administration significantly suppressed CNV volumes in the laser-induced model.
• Pemafibrate treatment activated PPARα downstream genes in both the liver and the eye, particularly in the RPE-choroid.
• Serum levels of fibroblast growth factor 21 (FGF21) were elevated, and triglyceride levels were reduced by pemafibrate.

Conclusions:

• Pemafibrate demonstrates a promising therapeutic potential for suppressing pathological CNV in the context of AMD.
• PPARα activation by pemafibrate may offer a novel approach to managing AMD by targeting CNV development.
• Further research into pemafibrate as a treatment for AMD-related CNV is warranted.