@article {313191,
	title = {Cytochrome P450-generated metabolites derived from ω-3 fatty acids attenuate neovascularization},
	journal = {Proc Natl Acad Sci U S A},
	volume = {111},
	number = {26},
	year = {2014},
	month = {2014 Jul 01},
	pages = {9603-8},
	abstract = {Ocular neovascularization, including age-related macular degeneration (AMD), is a primary cause of blindness in individuals of industrialized countries. With a projected increase in the prevalence of these blinding neovascular diseases, there is an urgent need for new pharmacological interventions for their treatment or prevention. Increasing evidence has implicated eicosanoid-like metabolites of long-chain polyunsaturated fatty acids (LCPUFAs) in the regulation of neovascular disease. In particular, metabolites generated by the cytochrome P450 (CYP)-epoxygenase pathway have been shown to be potent modulators of angiogenesis, making this pathway a reasonable previously unidentified target for intervention in neovascular ocular disease. Here we show that dietary supplementation with ω-3 LCPUFAs promotes regression of choroidal neovessels in a well-characterized mouse model of neovascular AMD. Leukocyte recruitment and adhesion molecule expression in choroidal neovascular lesions were down-regulated in mice fed ω-3 LCPUFAs. The serum of these mice showed increased levels of anti-inflammatory eicosanoids derived from eicosapentaenoic acid and docosahexaenoic acid. 17,18-epoxyeicosatetraenoic acid and 19,20-epoxydocosapentaenoic acid, the major CYP-generated metabolites of these primary ω-3 LCPUFAs, were identified as key lipid mediators of disease resolution. We conclude that CYP-derived bioactive lipid metabolites from ω-3 LCPUFAs are potent inhibitors of intraocular neovascular disease and show promising therapeutic potential for resolution of neovascular AMD.},
	keywords = {Animals, Arachidonic Acids, Choroidal Neovascularization, Chromatography, Liquid, Cytochrome P-450 Enzyme System, DNA, Complementary, Enzyme-Linked Immunosorbent Assay, Fatty Acids, Omega-3, Flow Cytometry, Food, Fortified, Immunoblotting, Laser Capture Microdissection, Macular Degeneration, Mice, PPAR gamma, Real-Time Polymerase Chain Reaction, Tandem Mass Spectrometry},
	issn = {1091-6490},
	doi = {10.1073/pnas.1401191111},
	author = {Yanai, Ryoji and Mulki, Lama and Hasegawa, Eiichi and Takeuchi, Kimio and Sweigard, Harry and Suzuki, Jun and Gaissert, Philipp and Vavvas, Demetrios G and Sonoda, Koh-Hei and Rothe, Michael and Schunck, Wolf-Hagen and Miller, Joan W and Connor, Kip M}
}
