BACKGROUND: 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.

METHODS: 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.

RESULTS: 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-. This inflammatory cytokine was found in a subset of microglia that was closely associated with retinal vessels.

CONCLUSION: 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.