Fenofibrate and diabetic retinopathy
Reviewed by Kurt Spiteri Cornish

Fenofibrate is an agonist of peroxisome proliferator-activated receptor-alpha (PPARα) which is used as a lipid-lowering agent. By reducing blood lipid levels, it can decrease retinal hard exudates which is beneficial in diabetic retinopathy (DR). FIELD and ACCORD studies show that beneficial effects on DR progression appear to be independent of its lipid-lowering properties and may be due to anti-inflammatory properties. In this study, cultured ARPE-19 cells (human retinal pigment epithelial cell line) from a diabetic rat model were used to assess the impact of fenofibrate on oxidate stress markers, autophagy-related proteins and tight junction integrity. High glucose conditions increased levels of reactive oxygen species (ROS) with increase in oxidative stress within retinal pigment epithelial (RPE) cells. This indicated higher susceptibility to apoptosis in RPE cells under diabetic conditions. There was a notable increase in expression of autophagy-related proteins indicating h8ened autophagic activity in RPE cells but despite this, there was disruption of tight junction proteins in RPE cells (which is crucial for maintaining the integrity of blood-retinal barrier). Fenofibrate administration resulted in a reduction of inflammatory markers, oxidative stress levels and decreased ROS production, which, in turn, promoted cell survival in the RPE under hyperglycaemic conditions. There was also enhancement of autophagic activity (increase in LC3 protein, for instance) which may contribute to cellular homeostasis and delay disease progression. There was also increased ferroptosis inhibition which prevented iron-mediated cell damage. In subsequent in vivo studies, fenofibrate helped maintain normal retinal structure leading to prevention of early retinal damage caused by diabetes. This study suggests that fenofibrate offers a multifaceted protective effect on the retina by addressing both oxidative stress and autophagic dysfunction in early-stage DR, as well as regulation of ferroptosis, a form of programmed cell death driven by iron accumulation and lipid peroxidation. Further investigation is warranted.

Fenofibrate exerts protective effects in diabetic retinopathy. 
Chen S, Wang X, Sun D, et al. 
CURRENT EYE RESEARCH 
2025;50(10):1010–8.