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

研究成果: Article査読

127 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1177-1185
ページ数9
ジャーナルGlia
58
10
DOI
出版ステータスPublished - 2010 8 1
外部発表はい

ASJC Scopus subject areas

  • 神経学
  • 細胞および分子神経科学

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