The development of the mammalian retinal vasculature involves angiogenesis and subsequent remodelling of a nascent plexus into the mature vascular tree. Vascular remodelling was previously thought to be mediated by either oxygen or T-cell-mediated endothelial cell apoptosis, but a role for astrocytes, a type of glial cell that undergo their own progression from precursor to immature to mature states, was unsuspected. Now, Li-Juan Duan and Guo-Hua Fong show that remodelling is regulated by oxygen sensing in astrocytes. By disrupting oxygen sensing in astrocyte precursors (via targeted deletion of the Phd2 gene that acts upstream of HIF-α), astrocytes were maintained in immature but proliferative states, therefore increasing their abundance. These changes are accompanied by a failure of normal vascular remodelling, increased endothelial cell proliferation, reduced endothelial cell apoptosis and a failure of vascular regression. Simply stimulating astrocyte proliferation with PDGF-A mimics the phenotype of astrocyte Phd2 deletion, suggesting that the abundance of astrocytes alone can account for the failure of vascular pruning. This work thus provides a mechanism by which oxygen plays into retinal angiogenesis via an astrocyte intermediate.
