April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
von Hippel Lindau Protein and Hypoxia Inducible Factor-2alpha Degradation in Astrocytes is Essential for Regression of the Hyaloidal Vasculature
Author Affiliations & Notes
  • Toshihide Kurihara
    Cell Biology,
    Scripps Research Institute, La Jolla, California
  • Peter D. Westenskow
    Cell Biology,
    Scripps Research Institute, La Jolla, California
  • Tim U. Krohne
    Cell Biology,
    Scripps Research Institute, La Jolla, California
  • Edith Aguilar
    Cell Biology,
    Scripps Research Institute, La Jolla, California
  • Randall S. Johnson
    Division of Biology, University of California, San Diego, La Jolla, California
  • Martin Friedlander
    Cell Biology MB28,
    Scripps Research Institute, La Jolla, California
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4836. doi:
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      Toshihide Kurihara, Peter D. Westenskow, Tim U. Krohne, Edith Aguilar, Randall S. Johnson, Martin Friedlander; von Hippel Lindau Protein and Hypoxia Inducible Factor-2alpha Degradation in Astrocytes is Essential for Regression of the Hyaloidal Vasculature. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4836.

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

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Abstract

Purpose: : Regression of the hyaloidal vasculature is a physiological process that signals the transition from embryonic to adult circulation in the retina. Recently, we found that molecular oxygen-sensing such as von Hippel Lindau Protein (VHL) and hypoxia-inducible factors (HIFs) in retinal neurons are required for this transition (Kurihara et al. Development 2010). In this study, we explored the contribution of VHL/HIF signaling in other cell types in the retina to this process.

Methods: : Transgenic mice expressing Cre recombinase specifically in astrocytes (GFAP-Cre mice), were mated with VHLfloxed/floxed mice, HIF-1afloxed/floxed mice HIF-2afloxed/floxed mice and/or VEGFfloxed/floxed mice to generate astrocyte-specific oxygen-sensing gene conditional knockout mice.

Results: : We demonstrate that a deficiency in degradation of HIFs by deletion of VHL is associated with accelerated hyaloidal vessel regression compared to wild type littermates in early neonatal stages despite upregulation of VEGF in the retina. After postnatal day 14, however, these mice exhibit massive secondary growth of hyaloidal vessels along the surface of the posterior lens capsule. Genetic deletion of HIF-2a or VEGF, but not HIF-1a, rescues the vascular phenotypes in the VHL; GFAP-Cre KO mice.

Conclusions: : These data suggest that the VHL/HIF-2a/VEGF pathway in astrocytes regulates the normal regression of the hyaloidal vasculature.

Keywords: astrocyte • hypoxia • retinal development 
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