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Lexi Ding, Rui Cheng, Yang Hu, Jian-Xing Ma; Therapeutic Effect of PPARα Agonist on Pericyte Loss in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):279.
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Purpose: Pericyte degeneration is an early event in diabetic retinopathy (DR) and plays an important role in retinal vascular leakage. Fenofibrate, a Peroxisome Proliferator-Activated Receptor α (PPARα) agonist, has been shown to have robust protective effects against DR. This study is to evaluate the efficacy and molecular mechanism of Fenofibrate on pericyte loss in DR.
Methods: Fenofibrate was administrated to streptozotocin (STZ)-induced diabetic Wistar rats at dose of 160 mg/kg/day for 2 months. Periodic acid schiff (PAS) and hematoxylin staining were performed to quantify pericyte loss and acellular capillaries in retina digestion samples. Palmitate, a saturated fatty acid, was used as a diabetic stressor in cultured primary human retinal capillary pericytes (HRCP). Cell viability was quantified by MTT assay, and apoptotic cells were measured by TUNEL assay . Intracellular ROS levels were measured by CM-H2DCFHDA. Western blot analysis was employed to measure changes of protein levels.
Results: Fenofibrate significantly decreased retinal pericyte loss and acellular capillaries in diabetic rat retina. Fenofibrate improved HRCP viability and protected the cells from palmitate-induced apoptosis. Fenofibrate decreased palmitate-induced ROS production and down-regulated NOX4 expression. Fenofibrate suppressed NF-kB activation and prevented the down-regulation of platelet-derived growth factor-B (PDGF-B) expression in HRCP after palmitate treatment. Furthermore, over-expression of PPARα had antioxidant and anti-inflammation effects in pericytes, similar to Fenofibrate.
Conclusions: Fenofibrate has therapeutic potential on retinal pericyte loss in DR and the effect is, at least in part, through activating PPARα.
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