2020
DOI: 10.3390/jcm10010126
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Fenofibrate Reduces the Severity of Neuroretinopathy in a Type 2 Model of Diabetes without Inducing Peroxisome Proliferator-Activated Receptor Alpha-Dependent Retinal Gene Expression

Abstract: Fenofibrate slows the progression of clinical diabetic retinopathy (DR), but its mechanism of action in the retina remains unclear. Fenofibrate is a known agonist of peroxisome proliferator-activated receptor alpha (PPARα), a transcription factor critical for regulating metabolism, inflammation and oxidative stress. Using a DR mouse model, db/db, we tested the hypothesis that fenofibrate slows early DR progression by activating PPARα in the retina. Relative to healthy littermates, six-month-old db/db mice exhi… Show more

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Cited by 12 publications
(9 citation statements)
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“…On the other hand, it is reported that PPARα is a key modulator of hepatic FGF21 [47]. This is consistent with our previous reports and other studies that PPARα agonists (pemafibrate or fenofibrate) increase serum levels of FGF21 as well as boost liver function to exert therapeutic effects in ischemic retinopathies such as diabetic retinopathy or ocular ischemic syndrome [27,30,31,48].…”
Section: Discussionsupporting
confidence: 92%
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“…On the other hand, it is reported that PPARα is a key modulator of hepatic FGF21 [47]. This is consistent with our previous reports and other studies that PPARα agonists (pemafibrate or fenofibrate) increase serum levels of FGF21 as well as boost liver function to exert therapeutic effects in ischemic retinopathies such as diabetic retinopathy or ocular ischemic syndrome [27,30,31,48].…”
Section: Discussionsupporting
confidence: 92%
“…In fact, we previously reported that pemafibrate maintained the amplitudes of OPs in a murine model of diabetes via maintaining the expression of synaptophysin, a marker of synapse [31]. Even though the expression of synaptophysin had a slight increase by pemafibrate administration, we assume that our current results have a consistency with the results in our previous study [31] and other PPARα studies [48,71].…”
Section: Discussionsupporting
confidence: 90%
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“…A recent report also demonstrated that fenofibrate reduced the severity of retinopathy in db/db mice (another mouse model of DR) without inducing PPARα-dependent gene expressions in the retina [94]. Rather, strong activation of PPARα in the liver was observed [94]. Taken together, further investigations on where PPARα activation exerts its therapeutic effects on DR are needed (Figure 2).…”
Section: Eye Diseasesmentioning
confidence: 96%
“…In this regard, therapeutic effects of pemafibrate on ocular neovascularization may be related to hepatic and systemic FGF21 induction. A recent report also demonstrated that fenofibrate reduced the severity of retinopathy in db/db mice (another mouse model of DR) without inducing PPARα-dependent gene expressions in the retina [94]. Rather, strong activation of PPARα in the liver was observed [94].…”
Section: Eye Diseasesmentioning
confidence: 99%