The astrocyte-expressed integrin αvβ8 governs blood vessel sprouting in the developing retina

The mouse retina is vascularized after birth when angiogenic blood vessels grow and sprout along a pre-formed latticework of astrocytes. How astrocyte-derived cues control patterns of blood vessel growth and sprouting, however, remains enigmatic. Here, we have used molecular genetic strategies in mice to demonstrate that alpha v beta 8 integrin expressed in astrocytes is essential for neovascularization of the developing retina. Selective ablation of alpha v or beta 8 integrin gene expression in astrocytes leads to impaired blood vessel sprouting and intraretinal hemorrhage, particularly during formation of the secondary vascular plexus. These pathologies correlate, in part, with diminished alpha v beta 8 integrin-mediated activation of extracellular matrix-bound latent transforming growth factor beta s (TGF beta s) and defective TGF beta signaling in vascular endothelial cells, but not astrocytes. Collectively, our data demonstrate that alpha v beta 8 integrin is a component of a paracrine signaling axis that links astrocytes to blood vessels and is essential for proper regulation of retinal angiogenesis.