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Astrocyte-Derived Vascular Endothelial Growth Factor Stabilizes Vessels in the Developing Retinal Vasculature

Scott, A; Powner, MB; Gandhi, P; Clarkin, C; Gutmann, DH; Johnson, RS; Ferrara, N; (2010) Astrocyte-Derived Vascular Endothelial Growth Factor Stabilizes Vessels in the Developing Retinal Vasculature. PLoS ONE , 5 (7) , Article e11863. 10.1371/journal.pone.0011863. Green open access

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Abstract

Vascular endothelial growth factor (VEGF) plays a critical role in normal development as well as retinal vasculature disease. During retinal vascularization, VEGF is most strongly expressed by not yet vascularized retinal astrocytes, but also by retinal astrocytes within the developing vascular plexus, suggesting a role for retinal astrocyte-derived VEGF in angiogenesis and vessel network maturation. To test the role of astrocyte-derived VEGF, we used Cre-lox technology in mice to delete VEGF in retinal astrocytes during development. Surprisingly, this only had a minor impact on retinal vasculature development, with only small decreases in plexus spreading, endothelial cell proliferation and survival observed. In contrast, astrocyte VEGF deletion had more pronounced effects on hyperoxia-induced vaso-obliteration and led to the regression of smooth muscle cell-coated radial arteries and veins, which are usually resistant to the vessel-collapsing effects of hyperoxia. These results suggest that VEGF production from retinal astrocytes is relatively dispensable during development, but performs vessel stabilizing functions in the retinal vasculature and might be relevant for retinopathy of prematurity in humans.

Type: Article
Title: Astrocyte-Derived Vascular Endothelial Growth Factor Stabilizes Vessels in the Developing Retinal Vasculature
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0011863
Publisher version: http://dx.doi.org/10.1371/journal.pone.0011863
Language: English
Additional information: © 2010 Scott et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: OXYGEN-INDUCED RETINOPATHY, MESSENGER-RNA STABILITY, BLOOD-VESSELS, VEGF EXPRESSION, CELL, HYPOXIA, PREMATURITY, SURVIVAL, MOUSE, MICE
UCL classification: 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 Pop Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
URI: https://discovery.ucl.ac.uk/id/eprint/1361004
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