1. Volume 29, Issue 1, Pages 1-7 (January 2013)
Lipoxins, resolvins, and protectins in the prevention and treatment of diabetic macular edema and retinopathy 
Undurti N. Das, M.D., F.A.M.S. 
Nutrition 
Volume 29, Issue 1, Pages 1-7 (January 2013)
DOI: /j.nut
Copyright © 2013 Elsevier Inc. Terms and Conditions

2. Fig. 1
Scheme showing possible relation among polyunsaturated fatty acids and their metabolites, TNF, VEGF, R\OS lipid peroxidation, and nitric oxide and their role in macular edema retinopathy. Hyperglycemia inhibits the activity of Δ-6 and Δ-5 desaturases that in turn decreases plasma and tissue levels of AA, EPA, and DHA, the precursors of lipoxins, resolvins, and protectins. Hyperglycemia activates leukocytes and macrophages. Activated leukocytes and macrophages release excess amounts of ROS that increase the lipid peroxidation process and decrease endothelial nitric oxide formation and release. ROS also inactivates nitric oxide. The increased generation of TNF-α and other proinflammatory cytokines by activated macrophages also produce increased amounts of ROS. The increased production of ROS, TNF-α, and lipid peroxides and the decreased generation of endothelial nitric oxide cause endothelial cell damage. This further interferes with the production of endothelial nitric oxide, a potent vasodilator, platelet antiaggregator, and inactivator of ROS. As a result, hypoxia sets in and triggers an increase in the production of VEGF, alters the Notch-1, Wnt-1, and HIF-1α pathways, and produces neovascularization. AA, EPA, DHA, lipoxins, resolvins, and protectins have potent anti-inflammatory action because they suppress leukocyte and macrophage activation, inhibit TNF-α production, prevent platelet aggregation, increase the production of endothelial nitric oxide, and are vasodilators. Thus, these bioactive lipids have negative feedback control on inflammation, ROS generation, and the lipid peroxidation process. Furthermore, EPA, DHA, lipoxins, resolvins, and protectins inhibit VEGF production, regulate the Notch-1, Wnt-1, and HIF-1α pathways, and thus decrease neovascularization. It is suggested that presence of adequate amounts of AA, EPA, DHA, lipoxins, resolvins, and protectins will prevent and/or even reverse the macular edema and pathologic retinopathy seen in diabetes mellitus, hypertension, retinopathy due to prematurity, and age-related macular degeneration. (−), decrease in synthesis, release, and/or action; (+), increase in synthesis, release, and/or action; AA, arachidonic acid; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; HIF-1α, hypoxia-inducible factor-1α; MO, macrophages; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-α; VEGF, vascular endothelial growth factor.
Nutrition  , 1-7DOI: ( /j.nut )
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