Abstract
Purpose: :
The new studies from The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) reported that oral administration of fenofibrate, a relativlye safe and low cost lipid-lowering drug, prevented the progression of diabetic retinopathy (DR) in type 2 diabetic patients. The purpose of this study is to evaluate if fenofibrate has therapeutic effects on DR in type 1 diabetes and if topical administration of fenofibrate is able to prevent DR in type 1 diabetes.
Methods: :
Human retinal endothelial cells (HRECs) were cultured on Matrigel or Transwell inserts in the presence or absence of various concentrations of fenofibrate, the effects of fenofibrate on tube formation and cell migration were evaluated. Oxygen-induced retinopathy (OIR) was generated by exposing newborn rats to 75% oxygen. Diabetes was induced in adult rats by injection of streptozotocin (STZ). Eyedrop containing 3% fenofibrate or control vehicle were topically administered to the cornea of OIR rats or diabetic rats 5 and 3 times a day, respectively. Levels of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) were measured by Western blot and enzyme-linked immunosorbent assay (ELISA). Retinal vascular leakage was evaluated by retinal vascular permeability assay, and retinal neovascularization (NV) was evaluated by fluorescein angiography.
Results: :
Fenofibrate inhibited HREC tube formation and cell migration. Topical application of fenofibrate significantly decreased retinal vascular permeability and reduced levels of VEGF and ICAM-1 in the retina from OIR rats and from STZ-induced diabetic rats, and arrested pre-retinal NV in the OIR rat model.
Conclusions: :
Fenofibrate attenuates retinal angiogenesis and inflammation, and topical administration of fenofibrate has therapeutic effects on DR in type 1 diabetes.
Keywords: diabetic retinopathy • clinical research methodology • retina