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A. J. Leedom, A. Sullivan, E. Zhu, D. Lau, K. Lam, K. Gronert; Increased Ratio of Dietary -3 Pufa Induces Formation of Dha-Derived Lipid Autacoids That Inhibit Inflammatory Neovascularization in the Cornea. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4956.
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Lipid autacoids are early response regulators of ocular inflammation and angiogenesis. Ongoing clinical trials test the long-standing notion that dietary ratios of ω-3 and ω-6 PUFA are determinants in the pathogenesis of ocular diseases. We set out to define how changes in ω-3 and ω-6 PUFA impact formation of lipid autacoids in the cornea, specifically ω-3 PUFA-derived autacoids.
Mice were placed on ω-3 or ω-6 PUFA diets for 3 months. Lipid autacoids were analyzed by LC/MS/MS-based lipidomics. Chronic inflammation and neovascularization was induced by placing silk sutures in the apex of corneas. Neovascularization was quantified by immuno-fluorescence using the endothelial marker CD31. PMN infiltration was quantified by measuring myeloperoxidase activity. Expression of inflammatory and angiogenic mediators was assessed by Real-Time PCR and Cytokine/Chemokine Array. Mice were treated post injury with selected DHA-derived autacoids (100 ng tid)for 7 days.
Formation of inflammatory and angiogenic lipid autacoids peaked 4 day post suture placement and remained elevated at day 7. Mice on the ω-6 PUFA diet demonstrated a 400 % increase in inflammatory neovascularization compared to a ω-3 deficient diet. Protection against inflammatory neovascularization correlated with formation of 17-HDHA, a metabolic marker for formation of DHA-derived resolvins and protectins, and abrogated PGE2 formation. Topical treatment with DHA-derived autacoids such as protectin D1 signifcantly inhibited neovascularization and formation of inflammatory and angiogenic mediators.
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