PPARγ Mediates a Direct Antiangiogenic Effect of ω3-PUFAs in Proliferative Retinopathy

Rationale: Omega3 long-chain polyunsaturated fatty acids (omega 3-PUFAs) are powerful modulators of angiogenesis. However, little is known about the mechanisms governing omega 3-PUFA-dependent attenuation of angiogenesis. Objective: This study aims to identify a major mechanism by which omega 3-PUFAs attenuate retinal neovascularization. Methods and Results: Administering omega 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)gamma almost completely abrogates this effect. Inhibition of PPAR gamma also reverses the omega 3-PUFA-induced reduction of retinal tumor necrosis factor-alpha, 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 gamma -mediated effect of omega 3-PUFAs on retinal neovascularization formation and retinal angiogenic activation that is independent of vascular endothelial growth factor. (Circ Res. 2010; 107: 495-500.)