Fenofibrate Ameliorates Oxidative Stress-Induced Retinal Microvascular Dysfunction in Diabetic Rats

The aim of this study is to investigate the effects of fenofibrate (FA) on microvascular dysfunction in the retina of diabetic rats, and to determine the underlying mechanism.

Streptozotocin (STZ)-induced diabetic rats and control rats were used in this study. A subgroup of STZ-induced diabetic rats was treated orally with vehicle or FA (100 mg/kg/day) for 24 weeks along with regular monitoring of body weight and serum parameters. At the end of the 24-week treatment, retinal vascular permeability was quantified by confocal microscopy using Evans blue as a tracer. Retinal capillary basement membrane thickness (BMT) was examined by transmission electron microscopy. The retinal reactive oxygen species (ROS) level was quantified by flow cytometry using a fluorescent probe. Levels of vascular endothelial growth factor (VEGF), nuclear facto (NF)-κB (p65), and thioredoxin interacting protein (TXNIP) were measured by Western blotting or enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction.

Retinal vascular permeability and BMT were significantly increased in diabetic rats compared to in non-diabetic control rats. Diabetes also increased the retinal ROS levels. These effects were associated with increased levels of VEGF, phosphorylation of p65(P-p65), and TXNIP. FA significantly ameliorated the retinal vascular permeability, alleviated retinal BMT, and reduced retinal ROS level. Consistent with these effects, FA also decreased VEGF and P-p65 expression and, at the same time, decreased TXNIP expression.

FA prevents the retinal microvascular dysfunction induced by diabetes, likely by restoring VEGF and P-p65 levels, and possibly by reducing oxidative stress and TXNIP expression.