An invited review following the soujinkai award : Cytochrome P450-generated metabolites of ω-3 fatty acids ameliorate choroidal neovascularization

Age-related macular degeneration (AMD) is the primary cause of blindness in elderly individuals of industrialized countries, with a projected 50% increase in prevalence by 2020. There is an urgent need for new nutritional or pharmacological interventions that are safe over the long term for the treatment or prevention of AMD. Prospective clinical studies have suggested that dietary intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) may protect against AMD. We recently characterized a mechanism by which dietary ω-3 LCPUFAs promote regression of choroidal neovessels in a well-characterized mouse model of neovascular AMD. The concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were increased in serum of mice fed a diet enriched in these ω-3 LCPUFAs. Cytochrome P450 enzymes catalyze the epoxidation of these primary ω-3 LCPUFAs to form 17,18-epoxyeicosatetraenoic acid and 19,20-epoxydocosapentaenoic acid, respectively, and intraperitoneal injection of these epoxyeicosanoids mimicked the beneficial effects of dietary ω-3 LCPUFAs on CNV resolution. Dietary intake of ω-3 PUFAs also suppressed leukocyte recruitment to CNV lesions by down-regulating endothelial expression of the adhesion molecules ICAM-1 and E-selectin as well as leukocyte expression of the ICAM-1 ligands CD11b and CD18. Bioactive lipid metabolites derived from ω-3 LCPUFAs thus show potential for the treatment or prevention of AMD.

ω-3 long-chain polyunsaturated fatty acids

cytochrome P450

choroidal neovascularization

immune cell recruitment