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Boyu Lu, Yang Hu, Scott Mitchell, Robert Mott, Qingjiong Zhang, Jianxing Ma, Ying Chen; Therapeutic Effect of Fenofibrate on Age Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4010.
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Recent FIELD studies showed that oral administration of fenofibrate, a safe and low-cost drug that lowers VLDL, has displayed impressive efficacy in slowing the progression of diabetic retinopathy (DR) in type 2 diabetic patients. As the progressive pathological changes of AMD are similar to that of DR, and as there are no studies in AMD, its effect on AMD has not been clear. The purpose of this study was to explore whether fenofibrate has therapeutic effect on AMD in laser induced CNV model.
REC were cultured on the Matrigel or Transwell inserts in the presence or absence of various doses of fenofibrate, and the effects of fenofibrate on tube formation and cell migration were evaluated. CNV models were generated by laser coagulation on adult rats.The chow containing fenofibrate and regular rodent chow were orally administered to laser induced CNV rats and their age-gender matched normal rats, respectively for 2 weeks. Levels of pro-inflammatory factors such as vascular endothelial cell growth factor (VEGF) and tumor necrosis factor-alpha (TNF-a) in the eyecup were measured by Western blot. Choroidal neovascularization (CNV) was evaluated by fluorescein angiography on flat mounted choroidal-RPE and by in vivo angiography. Retinal vascular permeability was measured by Evens blue analysis and by in vivo fundus angiography.
Fenofibrate inhibited REC tube formation and REC migration. Oral administration of fenofibrate downregulated VEGF and TNF-a expression, reduced vascular permeability, and ameliorated laser induced CNV in rat model.
Fenofibrate has direct impact on endothelial cells, and oral administration of fenofibrate has therapeutic effects on retinal inflammation and CNV in AMD model.
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