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Stabilization of the retinal vascular network by reciprocal feedback between blood vessels and astrocytes

West, H; Richardson, WD; Fruttiger, M; (2005) Stabilization of the retinal vascular network by reciprocal feedback between blood vessels and astrocytes. DEVELOPMENT , 132 (8) 1855 - 1862. 10.1242/dev.01732. Green open access

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Abstract

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.

Type: Article
Title: Stabilization of the retinal vascular network by reciprocal feedback between blood vessels and astrocytes
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.01732
Keywords: astrocytes, retina, blood vessels, PDGF-A, oxygen, transgenic mice, ENDOTHELIAL GROWTH-FACTOR, OPTIC-NERVE, VEGF EXPRESSION, OXYGEN-TENSION, SONIC-HEDGEHOG, CELL, DIFFERENTIATION, SURVIVAL, HYPOXIA, MOUSE
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/8484
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