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Ayumi Usui, Nobuyuki Ebihara; Bezafibrate downregulates the retinal microvascular inflammation.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5793.
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Bezafibrate (BZF) is a fibrate drug used as a lipid-lowering agent to treat hyperlipidemia. The results of randomized clinical trial have shown the beneficial effects of systemic fenofibrate therapy in reducing the progression of diabetic retinopathy independently of serum lipid levels. BZF is a pan-agonist for all subtypes of peroxisome proliferator-activated receptor (PPAR) such as PPARα, PPARγ, and PPARβ/δ. It has been reported PPARs play a key role in microvascular inflammation or angiogenesis. However, the effects of BZF in retinal cells remain unclear. The purpose of this study is to investigate the effects of BZF on retinal microvascular inflammation.
The primary human microvascular endothelial cells (HRMECs) and human RPE cell line (ARPE-19) were cultured. First, cytotoxicity and cell viability of BZF were assessed by CCK-8 assay and LDH activity assay. Next, we analyzed the effect of BZF(0,30,100μM) treatment on the expression of TNF-α–induced monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in HRMECs by real-time PCR and ELISA. And we analyzed the nuclear translocation of NFκB p65 subunit in BZF-treated HRMECs using TransAM NFκB kit® (Active Motif). IL-1β-induced Vascular Endothelial Growth Factor (VEGF) production in ARPE-19 was analyzed by real-time PCR and ELISA.
The cytotoxicity was significantly increased in HRMECs and ARPE-19 by treating with more than 200μM and 500μM of BZF, respectively. In HRMECs, the expression of TNF-α-induced MCP-1, ICAM-1 and VCAM-1 was significantly suppressed by BZF in a dose-dependent manner. TNF-α-induced nuclear translocation of NFκB p65 in HRMECs was also significantly decreased by BZF (p<0.01). Furthermore, IL1-β-induced VEGF production in RPE cells was also suppressed by BZF (p<0.01).
It is suggested that BZF has beneficial effects on retinal microvascular inflammation in the pathogenesis of diabetic retinopathy.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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