Abstract
Purpose: :
Choroidal neovascularization (CNV) is a severe complication of age-related macular degeneration (AMD). Recent studies have shown that fenofibrate, a potent PPAR-α agonist, has therapeutic effect on diabetic retinopathy. The purpose of this study is to evaluate the therapeutic effect of fenofibrate on laser-induced CNV.
Methods: :
Adult Brown Norway rats were photocoagulated using a diode laser to induce CNV. Immediately after the photocoagulation, laser-induced CNV rats were fed with fenofibrate chow or regular chow. Pro-angiogenic and pro-inflammatory factors in the eyecup were measure by Western blot analysis one week after photocoagulation with or without fenofibrate treatment. The fundus angiographs were examined at 1, 2 and 3 weeks post fenofibrate treatment, and the neovascular areas of lesions were quantified by FITC-dextran angiography on choroidal flat mount.
Results: :
Both of mRNA and protein levels of PPAR-α were significantly decreased in the eyecup of laser-induced CNV rats, as compared to those in un-treated controls, suggesting suppressed PPAR-α signaling. Fenofibrate treatment resulted in significant reductions of pro-angiogenesis and pro-inflammatory factor levels in the eyecup of the CNV rats, compared to the CNV group with normal diet group. Fenofibrate decreased pathologically vascular leakage from the CNV lesions and reduced the neovascular area in the laser-induced CNV rats.
Conclusions: :
The PPAR-α signaling pathway is down-regulated in laser-induced CNV rats, and fenofibrate has therapeutic effect on laser-induced CNV.
Keywords: choroid: neovascularization • age-related macular degeneration • laser