Effect of fenofibrate on retinal neurodegeneration in an experimental model of type 2 diabetes

Acta Diabetol. 2015 Feb;52(1):113-22. doi: 10.1007/s00592-014-0610-2. Epub 2014 Jul 17.


There is now consistent evidence from two major clinical trials (the Fenofibrate Intervention and Event Lowering in Diabetes and the Action to Control Cardiovascular Risk in Diabetes Eye) that fenofibrate arrests the progression of diabetic retinopathy in type 2 diabetic patients. However, the underlying mechanisms of this beneficial effect remain to be elucidated. The aim of the study was to evaluate the potential effect of fenofibric acid (FA), the active metabolite of fenofibrate, in preventing retinal neurodegeneration in an experimental mouse model of type 2 diabetes. For this purpose, we evaluated a total of 24 diabetic mice (db/db) aged 8 weeks that were randomly assigned to daily oral treatment (by gavage) with FA (100 mg/kg/day) (n = 12) or vehicle (n = 12) for 1 week. Ten non-diabetic mice (db/+) were used as control group. Retinal neurodegeneration was evaluated by measuring glial activation (immunofluorescence and Western blot) and apoptosis. Glutamate/aspartate transporter (GLAST) was assessed by immunofluorescence. Functional abnormalities were assessed by electroretinography (ERG). We observed that diabetic mice presented significantly higher glial activation and apoptosis in ganglion cell layer (GCL) than in age-matched non-diabetic mice. Treatment with FA resulted in a significant decrease in both glial activation and the rate of apoptosis in GCL in comparison with diabetic mice treated with vehicle. In addition, FA prevented GLAST downregulation induced by diabetes. Furthermore, a significant improvement of ERG parameters (oscillatory potential amplitudes and b-wave implicit time) was observed. We conclude that FA prevents retinal neurodegeneration induced by diabetes. Our results suggest that neuroprotection is one of the underlying mechanisms by which fenofibrate exerts its beneficial actions in diabetic retinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Retinopathy / drug therapy
  • Diabetic Retinopathy / etiology
  • Diabetic Retinopathy / physiopathology
  • Diabetic Retinopathy / prevention & control*
  • Disease Models, Animal
  • Excitatory Amino Acid Transporter 1 / metabolism
  • Fenofibrate / administration & dosage
  • Fenofibrate / analogs & derivatives*
  • Humans
  • Male
  • Mice
  • Retinal Degeneration / drug therapy
  • Retinal Degeneration / etiology
  • Retinal Degeneration / physiopathology
  • Retinal Degeneration / prevention & control*


  • Excitatory Amino Acid Transporter 1
  • Slc1a3 protein, mouse
  • fenofibric acid
  • Fenofibrate