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A. J. Leedom, L. Bellner, A. Sullivan, M. L. Schwartzman, K. Gronert; Dietary Polyunsaturated Fatty Acids Are Critical Regulators of Corneal Inflammatory Angiogenesis: A Role for DHA-derived Protective Lipid Autacoids. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1489.
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Western Diet contains 20 times the amount of ω-6 vs ω-3 PUFA and increased dietary intake of ω-6 PUFA has been linked to inflammatory and cardiovascular diseases. Resolution of inflammation is important to the cornea, as scarring and neovascularization are detrimental to vision. Eicosanoids are a family of ω-6 PUFA-derived autacoids, which also have important bioactions in the eye; these include mediating angiogenesis and inflammation. We set out to elucidate how acute changes in dietary ω-6 PUFA impacts formation of lipid autacoids and the sequelae of inflammatory angiogenesis in the cornea.
Mice were placed on a ω-6 PUFA, ω-3 PUFA or standard rodent diet for 3 months. Silk sutures were placed in the apex of mouse corneas. Neovascularization was quantified by vital microscopy and immuno-fluorescence using CD31 as an endothelial marker. Myeloperoxidase activity was selected as quantitative marker of PMN infiltration. Inflammatory/angiogenic markers were assessed by Western Blot, Real-Time PCR, Cytokine/Chemokine Array. Lipid autacoid profiles were analyzed by mass spectrometry-based lipidomics employing a triple quadrupole linear ion trap LC/MS/MS system.
Injured mouse corneas generate inflammatory and angiogenic eicosanoids (PGE2, PGD2, 5-HETE, 15-HETE, 12-HETE, 12-HETrE) as well as DHA-derived (ω-3) neuroprotectin D1 (NPD1) and 17-HDHA. Mice on the enriched ω-6 diet showed a dramatic shift in the lipid profile towards PGE2 formation with a concomitant loss of NPD1, while PGE2 formation in the ω-3 diet group was abrogated. Angiogenic responses in the ω-6 group were dramatically amplified, which was associated with increased formation of inflammatory/angiogenic factors. More importantly, topical treatment with NPD1 significantly inhibited inflammatory angiogenesis.
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