Abstract
Cardiovascular diseases lead to retinal ischemia, one of the leading causes of blindness. Retinal ischemia triggers pathological retinal glial responses and functional deficits. Therefore, maintaining retinal neuronal activities and modulating pathological gliosis may prevent loss of vision. Previously, pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, was nominated as a promising drug in retinal ischemia. However, a protective role of pemafibrate remains untouched in cardiovascular diseases-mediated retinal ischemia. Therefore, we aimed to unravel systemic and retinal alterations by treating pemafibrate in a new murine model of retinal ischemia caused by cardiovascular diseases. Adult C57BL/6 mice were orally administered pemafibrate (0.5 mg/kg) for 4 days, followed by unilateral common carotid artery occlusion (UCCAO). After UCCAO, pemafibrate was continuously supplied to mice until the end of experiments. Retinal function (a-and b-waves and the oscillatory potentials) was measured using electroretinography on day 5 and 12 after UCCAO. Moreover, the retina, liver, and serum were subjected to qPCR, immunohistochemistry, or ELISA analysis. We found that pemafibrate enhanced liver function, elevated serum levels of fibroblast growth factor 21 (FGF21), one of the neuroprotective molecules in the eye, and protected against UCCAO-induced retinal dysfunction, observed with modulation of retinal gliosis and preservation of oscillatory potentials. Our current data suggest a promising pemafibrate therapy for the suppression of retinal dysfunction in cardiovascular diseases.
Highlights
Ocular ischemic syndrome (OIS) is a vision-threatening disease caused by carotid artery stenosis or occlusion [1]
4 days of oral administration of pemafibrate, retinal ischemia was induced by occlusion of the right common carotid artery which is connected to the internal carotid artery stretched toward the ophthalmic artery (Figure A1)
We found that the body weight of adult male mice dramatically decreased 1 day after unilateral common carotid artery occlusion (UCCAO) (Figure A1)
Summary
Ocular ischemic syndrome (OIS) is a vision-threatening disease caused by carotid artery stenosis or occlusion [1]. The first case was reported in 1963 as a disease associated with internal carotid artery occlusion [2]. About 7.5 cases per million are annually diagnosed with OIS [3]. It is most common in old males, and patients with underlying diabetes, hypertension, and hyperlipidemia are more likely to have this disease. Carotid artery dissection, giant cell arteritis, and trauma can have high chances to cause OIS [5,6,7,8,9,10]. Precise mechanisms of OIS have not been fully unraveled yet
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