Ocular
ischemia is a common cause of
blindness and plays a detrimental role in various diseases such as
diabetic retinopathy, occlusion of central retinal arteries, and ocular ischemic syndrome. Abnormalities of neuronal activities in the eye occur under ocular ischemic conditions. Therefore, protecting their activities may prevent vision loss. Previously,
peroxisome proliferator-activated receptor alpha (PPARα) agonists were suggested as promising drugs in ocular
ischemia. However, the potential therapeutic roles of PPARα agonists in ocular
ischemia are still unknown. Thus, we attempted to unravel systemic and ocular changes by treatment of
fenofibrate, a well-known PPARα agonist, in a new murine model of ocular
ischemia. Adult mice were orally administered
fenofibrate (60 mg/kg) for 4 days once a day, followed by induction of ocular
ischemia by unilateral common carotid artery occlusion (UCCAO). After UCCAO,
fenofibrate was continuously supplied to mice once every 2 days during the experiment period. Electroretinography was performed to measure
retinal functional changes. Furthermore, samples from the retina, liver, and blood were subjected to qPCR, Western blot, or ELISA analysis. We found that
fenofibrate boosted liver function, increased serum levels of
fibroblast growth factor 21 (
FGF21), one of the neuroprotective molecules in the central nervous system, and protected against UCCAO-induced
retinal dysfunction. Our current data suggest a promising
fenofibrate therapy in ischemic retinopathies.