April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Increased Ratio of Dietary -3 Pufa Induces Formation of Dha-Derived Lipid Autacoids That Inhibit Inflammatory Neovascularization in the Cornea
A. J. Leedom; A. Sullivan; E. Zhu; D. Lau; K. Lam; K. Gronert
Author Affiliations & Notes
  • A. J. Leedom
    Pharmacology, New York Medical College, Valhalla, New York
    Center for Eye Disease and Development, University of California, Berkeley, Berkeley, California
  • A. Sullivan
    Center for Eye Disease and Development, University of California, Berkeley, Berkeley, California
  • E. Zhu
    Center for Eye Disease and Development, University of California, Berkeley, Berkeley, California
  • D. Lau
    Center for Eye Disease and Development, University of California, Berkeley, Berkeley, California
  • K. Lam
    Center for Eye Disease and Development, University of California, Berkeley, Berkeley, California
  • K. Gronert
    Center for Eye Disease and Development, University of California, Berkeley, Berkeley, California
  • Footnotes
    Commercial Relationships  A.J. Leedom, None; A. Sullivan, None; E. Zhu, None; D. Lau, None; K. Lam, None; K. Gronert, None.
  • Footnotes
    Support  EY016136
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4956. doi:
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      A. J. Leedom, A. Sullivan, E. Zhu, D. Lau, K. Lam, K. Gronert; Increased Ratio of Dietary -3 Pufa Induces Formation of Dha-Derived Lipid Autacoids That Inhibit Inflammatory Neovascularization in the Cornea. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4956.

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Abstract

Purpose: : Lipid autacoids are early response regulators of ocular inflammation and angiogenesis. Ongoing clinical trials test the long-standing notion that dietary ratios of ω-3 and ω-6 PUFA are determinants in the pathogenesis of ocular diseases. We set out to define how changes in ω-3 and ω-6 PUFA impact formation of lipid autacoids in the cornea, specifically ω-3 PUFA-derived autacoids.

Methods: : Mice were placed on ω-3 or ω-6 PUFA diets for 3 months. Lipid autacoids were analyzed by LC/MS/MS-based lipidomics. Chronic inflammation and neovascularization was induced by placing silk sutures in the apex of corneas. Neovascularization was quantified by immuno-fluorescence using the endothelial marker CD31. PMN infiltration was quantified by measuring myeloperoxidase activity. Expression of inflammatory and angiogenic mediators was assessed by Real-Time PCR and Cytokine/Chemokine Array. Mice were treated post injury with selected DHA-derived autacoids (100 ng tid)for 7 days.

Results: : Formation of inflammatory and angiogenic lipid autacoids peaked 4 day post suture placement and remained elevated at day 7. Mice on the ω-6 PUFA diet demonstrated a 400 % increase in inflammatory neovascularization compared to a ω-3 deficient diet. Protection against inflammatory neovascularization correlated with formation of 17-HDHA, a metabolic marker for formation of DHA-derived resolvins and protectins, and abrogated PGE2 formation. Topical treatment with DHA-derived autacoids such as protectin D1 signifcantly inhibited neovascularization and formation of inflammatory and angiogenic mediators.

Keywords: neovascularization • inflammation • cornea: basic science 
© 2009, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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