title: Short communication: PPAR gamma mediates a direct antiangiogenic effect of omega 3-PUFAs in proliferative retinopathy.
abstract: 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.
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Children's Hospital, Boston, Mass. 02115, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stahl
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Sapieha
authors.forename: Kip M
authors.initials: KM
authors.lastname: Connor
authors.forename: John Paul
authors.initials: JP
authors.lastname: Sangiovanni
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Aderman
authors.forename: Keirnan L
authors.initials: KL
authors.lastname: Willett
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Krah
authors.forename: Roberta J
authors.initials: RJ
authors.lastname: Dennison
authors.forename: Molly R
authors.initials: MR
authors.lastname: Seaward
authors.forename: Karen I
authors.initials: KI
authors.lastname: Guerin
authors.forename: Jing
authors.initials: J
authors.lastname: Hua
authors.forename: Lois E H
authors.initials: LE
authors.lastname: Smith
mesh_terms: 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
chemical_list: D020533:Angiogenesis Inhibitors; D015525:Fatty Acids, Omega-3; D047495:PPAR gamma; D042461:Vascular Endothelial Growth Factor A