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Rationale:
Omega3 long-chain polyunsaturated fatty acids (3-PUFAs) are powerful modulators of angiogenesis. However, little is known about the mechanisms governing 3-PUFA–dependent attenuation of angiogenesis.
Objective:
This study aims to identify a major mechanism by which 3-PUFAs attenuate retinal neovascularization.
Methods and Results:
Administering 3-PUFAs exclusively during the neovascular stage of the mouse model of oxygen-induced retinopathy induces a direct neovascularization reduction of more than 40% without altering vasoobliteration or the regrowth of normal vessels. Cotreatment with an inhibitor of peroxisome proliferator-activated receptor (PPAR) almost completely abrogates this effect. Inhibition of PPAR also reverses the 3-PUFA–induced reduction of retinal tumor necrosis factor-, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial selectin, and angiopoietin 2 but not vascular endothelial growth factor.
Conclusions:
These results identify a direct, PPAR-mediated effect of 3-PUFAs on retinal neovascularization formation and retinal angiogenic activation that is independent of vascular endothelial growth factor.
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