Short communication: PPAR gamma mediates a direct antiangiogenic effect of omega 3-PUFAs in proliferative retinopathy.
BACKGROUND
Omega3 long-chain polyunsaturated fatty acids (omega3-PUFAs) are powerful modulators of angiogenesis. However, little is known about the mechanisms governing omega3-PUFA-dependent attenuation of angiogenesis.


OBJECTIVE
This study aims to identify a major mechanism by which omega3-PUFAs attenuate retinal neovascularization.


RESULTS
Administering omega3-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 PPARgamma also reverses the omega3-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, PPARgamma-mediated effect of omega3-PUFAs on retinal neovascularization formation and retinal angiogenic activation that is independent of vascular endothelial growth factor.
Stahl
Andreas
A
Department of Ophthalmology, Harvard Medical School, Children's Hospital, Boston, Mass. 02115, USA.
Sapieha
Przemyslaw
P
Connor
Kip M
KM
Sangiovanni
John Paul
JP
Chen
Jing
J
Aderman
Christopher M
CM
Willett
Keirnan L
KL
Krah
Nathan M
NM
Dennison
Roberta J
RJ
Seaward
Molly R
MR
Guerin
Karen I
KI
Hua
Jing
J
Smith
Lois E H
LE
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000178:diet therapy / Q000378:metabolism* / Q000517:prevention & control; D047495:PPAR gamma / Q000502:physiology*; D012164:Retinal Diseases / Q000178:diet therapy / Q000378:metabolism* / Q000517:prevention & control; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D020533:Angiogenesis Inhibitors; D015525:Fatty Acids, Omega-3; D047495:PPAR gamma; D042461:Vascular Endothelial Growth Factor A