The astrocyte-expressed integrin alphavbeta8 governs blood vessel sprouting in the developing retina.

摘要

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 alphavbeta8 integrin expressed in astrocytes is essential for neovascularization of the developing retina. Selective ablation of alphav or beta8 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 alphavbeta8 integrin-mediated activation of extracellular matrix-bound latent transforming growth factor betas (TGFbetas) and defective TGFbeta signaling in vascular endothelial cells, but not astrocytes. Collectively, our data demonstrate that alphavbeta8 integrin is a component of a paracrine signaling axis that links astrocytes to blood vessels and is essential for proper regulation of retinal angiogenesis.