April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Resveratrol Inhibits Pathological Angiogenesis in the Vldlr Knockout Mouse Model of Retinal Neovascularization
J. Hua; K. I. Guerin; J. Chen; P. Sapieha; A. Stahl; K. Connor; N. M. Krah; R. J. Dennison; M. R. Seaward; L. E. H. Smith
Author Affiliations & Notes
  • J. Hua
    Ophthalmology, Harvard Medical School/Children's Hospital Boston, Boston, Massachusetts
  • K. I. Guerin
    Ophthalmology, Harvard Medical School/Children's Hospital Boston, Boston, Massachusetts
  • J. Chen
    Ophthalmology, Harvard Medical School/Children's Hospital Boston, Boston, Massachusetts
  • P. Sapieha
    Ophthalmology, Harvard Medical School/Children's Hospital Boston, Boston, Massachusetts
  • A. Stahl
    Ophthalmology, Harvard Medical School/Children's Hospital Boston, Boston, Massachusetts
    University Eye Hospital Freiburg, Freiburg, Germany
  • K. Connor
    Ophthalmology, Harvard Medical School/Children's Hospital Boston, Boston, Massachusetts
  • N. M. Krah
    Ophthalmology, Harvard Medical School/Children's Hospital Boston, Boston, Massachusetts
  • R. J. Dennison
    Ophthalmology, Harvard Medical School/Children's Hospital Boston, Boston, Massachusetts
  • M. R. Seaward
    Ophthalmology, Harvard Medical School/Children's Hospital Boston, Boston, Massachusetts
  • L. E. H. Smith
    Ophthalmology, Harvard Medical School/Children's Hospital Boston, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  J. Hua, None; K.I. Guerin, None; J. Chen, None; P. Sapieha, None; A. Stahl, None; K. Connor, None; N.M. Krah, None; R.J. Dennison, None; M.R. Seaward, None; L.E.H. Smith, None.
  • Footnotes
    Support  NIH grant (EY08670, EY14811, to L.E.H.S), MACTEL Foundation (to L.E.H.S)
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3345. doi:
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      J. Hua, K. I. Guerin, J. Chen, P. Sapieha, A. Stahl, K. Connor, N. M. Krah, R. J. Dennison, M. R. Seaward, L. E. H. Smith; Resveratrol Inhibits Pathological Angiogenesis in the Vldlr Knockout Mouse Model of Retinal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3345.

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Abstract

Purpose: : Subretinal pathological neovascularization (NV) is the hallmark of wet age-related macular degeneration and other ocular diseases such as juxafoveal telangiectasia. Mice lacking the very low density lipoprotein receptor (VLDLR -/-) mimic these human ocular phenotypes and are a suitable model for studying NV. Resveratrol is a natural dietary polyphenol compound extacted from plants, and reported to inhibit tumor angiogenesis in vivo via oral administration. We investigated the anti-angiogenic effects of oral resveratrol treatment on ocular NV in VLDLR -/- mice, to evaluate its therapeutic potential.

Methods: : From postnatal day 10 (P10) to P30 (early intervention), VLDLR -/- pups were gavaged daily with resveratrol at 1g/kg bodyweight. Littermate controls received an identical volume of vehicle. In a second experimental paradigm, P21 mice were fed with 2.4g/kg resveratrol for 39 days (late intervention). At P30 or P60, respectively, retinas were flat-mounted to assess the subretinal NV. RNA and protein were extracted from the retinas for RT-qPCR, Western Blot and ELISA. Aortas of VLDLR -/- mice were isolated for an aortic ring assay with or without resveratrol treatment.Results: The pathological NV in VLDLR -/- originates in the deep vascular plexus around P15 and progressively invades the photoreceptor layer of retina towards the subretinal space. mRNA and protein analysis showed significant up-regulation of bFGF in the retinas of both P30 and P60 VLDLR -/- mice. Both early and late interventions with resveratrol significantly reduced the number of abnormal subretinal vessel sprouts in the VLDLR -/- mice (early

Conclusions: : Oral intake of resveratrol strongly reduces the number of abnormal subretinal vessels in VLDLR -/- mice, indicating that resveratrol is a promising candidate for treatment of ocular angiogenic diseases.

Keywords: retinal neovascularization • antioxidants • lipids 
© 2010, 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 © 2023 Association for Research in Vision and Ophthalmology.
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