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C.M. Aderman, K.M. Connor, Z. Kachra, J. Chen, J.X. Kang, L.E. H. Smith; Increased –3 / –6 Fatty Acid Ratio in Fat–1 Expressing Mice Protects Against Neovascularization in Oxygen Induced Retinopathy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1429.
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ω–3 long chain polyunsaturated fatty acids (LCPUFAs), not normally synthesized in mammals, are essential dietary fats found mainly in fish oils. They may have important signaling roles in angiogenesis. The Caenorhabditis elegans fat–1 gene encodes an ω–3 desaturase that converts ω–6 to ω–3 fatty acids. Transgenic mice expressing this gene have a decreased ratio of ω–6 to ω–3 fatty acids compared with wild–type mice raised on an identical diet. Normally, this ratio is about 50:1, but in fat–1 expressing mice it falls to about 1:1. Using the mouse model of oxygen–induced retinopathy, we examined the effect of increased ω–3 fatty acid levels on proliferative retinopathy in vivo.
Fat–1 expressing mice fed a modified rodent diet, containing elevated levels of ω–6 LCPUFAs and no ω–3 fatty acids, were exposed to 75% O2 from P7 through P12. Mice were sacrificed at P17 and eyes were enucleated. Isolated retinas were stained with lectin and flatmounted for visualization with confocal microscopy. Vaso–obliteration and neovascular tuft areas were quantified and compared with values for retinas from age–matched wild type control mice with identical feed and oxygen conditions.
At P17 wild type mice lacking the fat–1 gene had extensive retinal vaso–obliteration (11.3% of total retinal area) and neovascular tuft formation (8.3%). Retinas from P17 Fat–1 homozygote mice, however, had significantly less vascular obliteration (4.9%, p=0.0001) and dramatically reduced neovascular tuft formation (4.3%, p=0.0002) when compared to wild type mice.
A decreased ω–6 to ω–3 LCPUFA ratio results in protection from retinal vaso–obliteration and therefore suppression of neovascularization. These findings introduce possible therapeutic approaches for proliferative retinopathies in the form of simple dietary modifications with enriched ω–3 fatty acid content.
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