Letter abstract
Nature Medicine 13, 868 - 873 (2007)
Published online: 24 June 2007 | doi:10.1038/nm1591
Increased dietary intake of 
-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis
Kip M Connor1,9, John Paul SanGiovanni2,9, Chatarina Lofqvist1,3, Christopher M Aderman1, Jing Chen1, Akiko Higuchi1, Song Hong4, Elke A Pravda1, Sharon Majchrzak5, Deborah Carper6, Ann Hellstrom7, Jing X Kang8, Emily Y Chew2, Norman Salem, Jr5, Charles N Serhan4 & Lois E H Smith1
Many sight-threatening diseases have two critical phases, vessel loss followed by hypoxia-driven destructive neovascularization. These diseases include retinopathy of prematurity and diabetic retinopathy, leading causes of blindness in childhood and middle age affecting over 4 million people in the United States. We studied the influence of 
-3- and -6-polyunsaturated fatty acids (PUFAs) on vascular loss, vascular regrowth after injury, and hypoxia-induced pathological neovascularization in a mouse model of oxygen-induced retinopathy1. We show that increasing -3-PUFA tissue levels by dietary or genetic means decreased the avascular area of the retina by increasing vessel regrowth after injury, thereby reducing the hypoxic stimulus for neovascularization. The bioactive -3-PUFA-derived mediators neuroprotectinD1, resolvinD1 and resolvinE1 also potently protected against neovascularization. The protective effect of -3-PUFAs and their bioactive metabolites was mediated, in part, through suppression of tumor necrosis factor-
. This inflammatory cytokine was found in a subset of microglia that was closely associated with retinal vessels. These findings indicate that increasing the sources of -3-PUFA or their bioactive products reduces pathological angiogenesis. Western diets are often deficient in -3-PUFA, and premature infants lack the important transfer from the mother to the infant of -3-PUFA that normally occurs in the third trimester of pregnancy2. Supplementing -3-PUFA intake may be of benefit in preventing retinopathy.
- Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
- Division of Epidemiology and Clinical Research, National Eye Institute, 10 Center Drive, Bethesda, Maryland 20892, USA.
- Department of Pediatrics, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
- Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
- Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, 12420 Parklawn Drive, Rockville, Maryland 20892, USA.
- Office of the Director, National Eye Institute, 31 Center Drive, Bethesda, Maryland 20892, USA.
- Dept of Clinical Neurosciences, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
- Department of Medicine, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
- These authors contributed equally to this work.
Correspondence to: Lois E H Smith1 e-mail: lois.smith@childrens.harvard.edu
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