Prevention and treatment research of fenofibrate for diabetic retinopathy and its clinical translation

Diabetes is a worldwide prevalent disease and diabetic retinopathy (DR) is one of the common complications, which is vision threatening and even leading to blindness.The current management of DR includes laser retina photocoagulation, vitrectomy, and frequent intravitreal anti-vascular endothelial growth factor (VEGF) agents.However, these measures do not target the root cause and their efficacy is limited.Fenofibrate is a blood lipid lowering therapeutics and its metabolite, fenofibric acid, is responsible for the pharmacology effect.Two large clinical trials (FIELD and ACCORD-Eye) have demonstrated oral fenofibrate retarded progression of DR and the needs for laser retinopexy.The animal and cell researches have revealed that fenofibric acid attenuated overexpression of basement membrane and VEGF, protected the tight junctions of endothelial cells and vascular permeability, as well as inhibited cells migration and neovascularization via suppression of inflammatory cytokines.These pharmacological effects might be materialized through several pathways, such as PPAR-α, MAPK and nuclear factor-κB (NF-кB). Blood-ocular barrier is a significant limiting factor for therapeutics reaching retina after systemic administration.Local ocular application of fenofibric acid may achieve better efficacy through improving therapeutic concentration in the eye.This drug may be delivered either by eye drop formulation or a sustained delivery device under conjunctiva or sub-Tenon.