Astrocyte hypoxic response is essential for pathological but not developmental angiogenesis of the retina

Alexander Weidemann, Tim U. Krohne, Edith Aguilar, Toshihide Kurihara, Norihiko Takeda, Michael I. Dorrell, M. Celeste Simon, Volker H. Haase, Martin Friedlander, Randall S. Johnson

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Vascular/parenchymal crosstalk is increasingly recognized as important in the development and maintenance of healthy vascularized tissues. The retina is an excellent model in which to study the role of cell type-specific contributions to the process of blood vessel and neuronal growth. During retinal vascular development, glial cells such as astrocytes provide the template over which endothelial cells migrate to form the retinal vascular network, and hypoxia-regulated vascular endothelial growth factor (VEGF) has been demonstrated to play a critical role in this process as well as pathological neovascularization. To investigate the nature of cell-specific contributions to this process, we deleted VEGF and its upstream regulators, the hypoxia-inducible transcription factors HIF-1α and HIF-2α, and the negative regulator of HIFa, von Hippel-Lindau protein (VHL), in astrocytes. We found that loss of hypoxic response and VEGF production in astrocytes does not impair normal development of retinal vasculature, indicating that astrocyte-derived VEGF is not essential for this process. In contrast, using a model of oxygen-induced ischemic retinopathy, we show that astrocyte-derived VEGF is essential for hypoxia-induced neovascularization. Thus, we demonstrate that astrocytes in the retina have highly divergent roles during developmental, physiological angiogenesis, and ischemia-driven, pathological neovascularization.

Original languageEnglish
Pages (from-to)1177-1185
Number of pages9
JournalGlia
Volume58
Issue number10
DOIs
Publication statusPublished - 2010 Aug 1
Externally publishedYes

Keywords

  • Astrocytes
  • Hypoxia-inducible factor
  • Hypoxic response
  • Retinal angiogenesis
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Weidemann, A., Krohne, T. U., Aguilar, E., Kurihara, T., Takeda, N., Dorrell, M. I., Simon, M. C., Haase, V. H., Friedlander, M., & Johnson, R. S. (2010). Astrocyte hypoxic response is essential for pathological but not developmental angiogenesis of the retina. Glia, 58(10), 1177-1185. https://doi.org/10.1002/glia.20997