gms | German Medical Science

23rd Annual Meeting of the German Retina Society

German Retina Society

24.09. - 25.09.2010, Freiburg

Lipid-derived angiogenic modulators: mechanistic investigations of ω3-PUFA effects in proliferative retinopathies

Meeting Abstract

  • Andreas Stahl - Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston (USA); University Eye Clinic Freiburg
  • P. Sapieha - Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston (USA); Faculty of Medicine, University of Montréal (CA)
  • J. Chen - Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston (USA)
  • J.P. SanGiovanni - Division of Epidemiology and Clinical Research, National Eye Institute, Bethesda (USA)
  • M.R. Seaward - Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston (USA)
  • K.L. Willett - Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston (USA)
  • R.J. Dennison - Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston (USA)
  • N.M. Krah - Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston (USA)
  • C.M. Aderman - Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston (USA)
  • Y. Kanaoka - Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston (USA)
  • K. Gronert - Vision Science Program, University of California, Berkeley (USA)
  • L.E.H. Smith - Department of Ophthalmology, Harvard Medical School, Children's Hospital Boston (USA)

German Retina Society. 23rd Annual Conference of the German Retina Society. Freiburg i. Br., 24.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc10rg56

DOI: 10.3205/10rg56, URN: urn:nbn:de:0183-10rg560

This is the translated version of the article.
The original version can be found at: http://www.egms.de/de/meetings/rg2010/10rg56.shtml

Published: September 21, 2010

© 2010 Stahl et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Background: VEGF-inhibitors have revolutionized the clinical treatment of angiogenic eye diseases. Similarly, lipid-derived angiogenic modulators have also been found to attenuate retinal neovascularization, but are mechanistically less well understood.

Methods: The effect of ω3-PUFAs on retinal angiogenesis was studied using the mouse model of oxygen-induced retinopathy (OIR). Mechanistic investigations were performed using various transgenic mouse strains and were validated with specific pharmacological inhibitors in vitro and in vivo.

Results: Supplementing ω3-PUFAs reduces retinal neovascularization by more than 40% in the OIR mouse model, similar to the effect seen with VEGF inhibition. The anti-angiogenic effect of ω3-PUFAs is abrogated in mice lacking the lipid metabolizing enzyme 5-lipoxygenase (5-Lox-/-). Among other functions, 5-Lox is essential for generating the anti-angiogenic lipid metabolite 4-HDHA, which binds to the nuclear receptor PPARγ and changes the gene expression profile of activated retinal endothelial cells to induce a less angiogenic state.

Conclusions: These results identify some critical steps in the mechanism of anti-angiogenic lipid signaling in the retina. Interestingly, the identified signaling cascade ω3-PUFA → 5-Lox enzyme → 4-HDHA metabolite → PPARγ receptor is independent of VEGF and may thus have additive effects clinically.