April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Dietary supplementation of ω-3 long chain polyunsaturated fatty acids promote choroidal neovessel resolution
Author Affiliations & Notes
  • Ryoji Yanai
    Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA
    Ophthalmology, Yamaguchi Univ Grad Sch of Med, Ube City, Japan
  • Lama Mulki
    Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA
  • Eiichi Hasegawa
    Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA
  • Kimio Takeuhi
    Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA
  • Harry Sweigard
    Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA
  • Jun Suzuki
    Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA
  • Demetrios G Vavvas
    Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA
  • Koh-hei Sonoda
    Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA
  • Joan W Miller
    Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA
  • Kip M Connor
    Ophthalmology, Harvard Medical School, Massachusetts Eye & Ear Infirmary, Boston, MA
  • Footnotes
    Commercial Relationships Ryoji Yanai, None; Lama Mulki, None; Eiichi Hasegawa, None; Kimio Takeuhi, None; Harry Sweigard, None; Jun Suzuki, None; Demetrios Vavvas, None; Koh-hei Sonoda, None; Joan Miller, Alcon (C), Imagen Biotech, Inc. (C), ISIS Pharmaceuticals, Inc. (C), KalVista Pharmaceuticals (C), Maculogix, Inc. (C), Massachusetts Eye and Ear Infirmary (P), ONL Therapeutics, LLC (C), Regeneron Pharmaceuticals, Inc. (C); Kip Connor, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1262. doi:
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      Ryoji Yanai, Lama Mulki, Eiichi Hasegawa, Kimio Takeuhi, Harry Sweigard, Jun Suzuki, Demetrios G Vavvas, Koh-hei Sonoda, Joan W Miller, Kip M Connor; Dietary supplementation of ω-3 long chain polyunsaturated fatty acids promote choroidal neovessel resolution. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1262.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: AMD is the primary cause of blindness in elderly individuals of industrialized countries. Clinical studies have indicated that dietary intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) may have a protective effect against AMD. This study characterizes the effects of dietary intake of ω-3 and ω-6 LCPUFAs in a mouse model of AMD.

Methods: The present studies adhered to ARVO’s Statement for the Use of Animals in Ophthalmic and Vision Research. C57BL/6 mice were fed a diet enriched with either ω-3 or ω-6 LCPUFAs for 2 weeks prior to choroidal neovascularization (CNV) induction by photocoagulation using a 532-nm laser. CNV development was evaluated by FA, SD-OCT, and choroidal flatmount (CFM). The primary eicosanoids and their downstream metabolites were analyzed by LC MS/MS lipidomics. Expression of ICAM-1, E-selectin, and VEGF in the retina, choroid, or laser-captured CNV were evaluated by RTPCR and immunoblot analysis. Macrophage invasion was evaluated in Cx3cr1GFP/+ mice. Leukocyte rolling velocity was analyzed using the autoperfused microflow chamber assay.

Results: Both OCT and CFM revealed the CNV size was significantly reduced, and FA grading showed significantly less leakage in the ω-3-fed-mice compared with the ω-6-fed mice. The concentrations of the principal ω-3 LCPUFAs (EPA and DHA) were significantly increased and the AA-derived eicosanoids were significantly reduced in the serum of ω-3-fed mice. Additionally the serum levels of EPA-derived and DHA-derived CYP450 eicosanoids were significantly increased in ω-3-fed mice. The mRNA expression and abundance of protein of ICAM-1 and E-selectin in the retina or choroid after CNV induction were significantly reduced in ω-3-fed mice. The rolling velocity of leucocytes in chambers coated with P-selectin and ICAM-1 was significantly greater in ω-3-fed mice. The abundance of VEGF protein in both the retina and choroid was significantly reduced in ω-3-fed mice.

Conclusions: We demonstrate that dietary supplementation with ω-3 LCPUFAs mediates choroidal neovessel regression. A clear understanding of the mechanisms of these molecules in AMD could bring a major shift in our approach to disease treatment. There is an unmet need for safe nutritional or pharmacological interventions for the treatment and ideally the prevention of AMD.

Keywords: 412 age-related macular degeneration • 583 lipids • 453 choroid: neovascularization  
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