Astrocyte-derived vascular endothelial growth factor stabilizes vessels in the developing retinal vasculature

Connon, Che John, Scott, Andrew, Powner, Michael B., Gandhi, Pranita, Clarkin, Claire, Gutmann, David H., Johnson, Randall S., Ferrara, Napoleone and Fruttiger, Marcus (2010) Astrocyte-derived vascular endothelial growth factor stabilizes vessels in the developing retinal vasculature. PLoS ONE, 5, (7), e11863. (doi:10.1371/journal.pone.0011863).


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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.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1371/journal.pone.0011863
ISSNs: 1932-6203 (print)
Related URLs:
Subjects: R Medicine > R Medicine (General)
Divisions : Faculty of Natural and Environmental Sciences > Biological Sciences > Biomedicine
ePrint ID: 339882
Accepted Date and Publication Date:
29 July 2010Published
Date Deposited: 31 May 2012 16:56
Last Modified: 31 Mar 2016 14:29

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