Omega3 long-chain polyunsaturated fatty acids (ω3-PUFAs) are powerful modulators of angiogenesis. However, little is known about the mechanisms governing ω3-PUFA–dependent attenuation of angiogenesis.

This study aims to identify a major mechanism by which ω3-PUFAs attenuate retinal neovascularization.

Administering ω3-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)γ almost completely abrogates this effect. Inhibition of PPARγ also reverses the ω3-PUFA–induced reduction of retinal tumor necrosis factor-α, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial selectin, and angiopoietin 2 but not vascular endothelial growth factor.

These results identify a direct, PPARγ-mediated effect of ω3-PUFAs on retinal neovascularization formation and retinal angiogenic activation that is independent of vascular endothelial growth factor.