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
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:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      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.

      Download citation file:


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

      ×
  • Supplements
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 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×