Increased dietary intake of ω-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis

Kip M. Connor, John Paul Sangiovanni, Chatarina Lofqvist, Christopher M. Aderman, Jing Chen, Akiko Higuchi, Song Hong, Elke A. Pravda, Sharon Majchrzak, Deborah Carper, Ann Hellstrom, Jing X. Kang, Emily Y. Chew, Norman Salem, Charles N. Serhan, Lois E.H. Smith

Research output: Contribution to journalArticlepeer-review

595 Scopus citations


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 ω-3- and ω-6- polyunsaturated fatty acids (PUFAs) on vascular loss, vascular regrowth after injury, and hypoxia-induced pathological neovascularization in a mouse model of oxygen-induced retinopathy. We show that increasing ω-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 ω-3-PUFA-derived mediators neuroprotectinD1, resolvinD1 and resolvinE1 also potently protected against neovascularization. The protective effect of ω-3-PUFAs and their bioactive metabolites was mediated, in part, through suppression of tumor necrosis factor-α. 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 ω-3-PUFA or their bioactive products reduces pathological angiogenesis. Western diets are often deficient in ω-3-PUFA, and premature infants lack the important transfer from the mother to the infant of ω-3-PUFA that normally occurs in the third trimester of pregnancy. Supplementing ω-3-PUFA intake may be of benefit in preventing retinopathy.

Original languageEnglish (US)
Pages (from-to)868-873
Number of pages6
JournalNature Medicine
Issue number7
StatePublished - Jul 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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