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First published online March 24, 2005
doi: 10.1242/10.1242/dev.01732

Development 132, 1855-1862 (2005)
Published by The Company of Biologists 2005
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Stabilization of the retinal vascular network by reciprocal feedback between blood vessels and astrocytes

Heloise West1,2, William D. Richardson1,3 and Marcus Fruttiger1,3,*,{dagger}

1 The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK
2 MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK
3 Department of Biology, University College London, Gower Street, London WC1E 6BT, UK

{dagger} Author for correspondence (e-mail: m.fruttiger{at}ucl.ac.uk)

Accepted 2 February 2005

Development of the retinal vasculature is controlled by a hierarchy of interactions among retinal neurons, astrocytes and blood vessels. Retinal neurons release platelet-derived growth factor (PDGFA) to stimulate proliferation of astrocytes, which in turn stimulate blood vessel growth by secreting vascular endothelial cell growth factor (VEGF). Presumably, there must be counteractive mechanisms for limiting astrocyte proliferation and VEGF production to prevent runaway angiogenesis. Here, we present evidence that the developing vessels provide feedback signals that trigger astrocyte differentiation – marked by cessation of cell division, upregulation of glial fibrillary acidic protein (GFAP) and downregulation of VEGF. We prevented retinal vessel development by raising newborn mice in a high-oxygen atmosphere, which leads, paradoxically, to retinal hypoxia (confirmed by using the oxygen-sensing reagent EF5). The forced absence of vessels caused prolonged astrocyte proliferation and inhibited astrocyte differentiation in vivo. We could reproduce these effects by culturing retinal astrocytes in a low oxygen atmosphere, raising the possibility that blood-borne oxygen itself might induce astrocyte differentiation and indirectly prevent further elaboration of the vascular network.

Key words: Astrocytes, Retina, Blood vessels, PDGF-A, Oxygen, Transgenic mice


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