The primary cause of blindness in elderly individuals of industrialized countries is age-related macular degeneration (AMD), which is characterized by blood vessel growth, or choroidal neovascularization (CNV). The prevalence of the disease is projected to increase 50% by the year 2020. There is an urgent need for new pharmacological interventions for the treatment and prevention of AMD.
Researchers from Massachusetts Eye and Ear/Schepens Eye Research Institute, Harvard Medical School and other institutions have demonstrated for the first time that the omega (ω)-3 long-chain polyunsaturated fatty acids (LCPUFAs), DHA and EPA, and their specific bioactive products derived from the cytochrome P450 (CYP) pathway, can influence choroidal neovascularization (CNV) and vascular leakage by modulating micro-environmental immune cell recruitment to the site of these lesions. Their findings will be published in PNAS Online Early Edition the week of June 16-20, 2014.
"These are the first results showing that omega (ω)-3 LCPUFAs and their CYP derived metabolites can regulate choroidal angiogenesis in vivo. The fact that this can be accomplished with physiologically relevant naturally occurring lipid metabolites is of significant clinical interest as these molecules are readily available and considered to be safe. Our findings not only show promising therapeutic potential for resolution of neovascular AMD, but also for other conditions or diseases that involve pathologic angiogenesis and inflammation," said Kip Connor, Ph.D., Assistant Professor in Ophthalmology at Harvard Medical School and senior author of the paper.
The researchers demonstrated that dietary supplementation of omega (ω)-3 long-chain polyunsaturated fatty acids (LCPUFAs) mediates choroidal neovessel regression in a well-characterized murine model of neovascular AMD. The cytochrome P450 (CYP) enzymes catalyze the epoxidation of these ω-3 LCPUFAs to form the eicosanoids 17,18-epoxyeicosatetraenoic acid (EEQ) and 19,20-epoxydocosapentaenoic acid (EDP), which were identified as key lipid mediators of disease resolution.Their findings show promising therapeutic potential in AMD disease resolution.
"Given the prevalence of neovascular eye disease, the potential impact of this study is highly significant. We have identified unique endogenous lipid biometabolites that are able to inhibit pathologic retinal angiogenesis, a major driver of vision loss worldwide. It is our hope that future studies will allow us to develop specific therapeutics that harness this knowledge resulting in a greater visual outcome and quality of life for patients suffering from these sight-threatening diseases," said lead author Ryoji Yanai, M.D., Ph.D.