PDGF Mediates a Neuron–Astrocyte Interaction in the Developing Retina

Abstract

Astrocytes invade the developing retina from the optic nerve head, over the axons of retinal ganglion cells (RGCs). RGCs express the platelet-derived growth factor A-chain (PDGF-A) and retinal astrocytes the PDGF alpha-receptor (PDGFR alpha), suggesting that PDGF mediates a paracrine interaction between these cells. To test this, we inhibited PDGF signaling in the eye with a neutralizing anti-PDGFR alpha antibody or a soluble extracellular fragment of PDGFR alpha. These treatments inhibited development of the astrocyte network. We also generated transgenic mice that overexpress PDGF-A in RGCs. This resulted in hyperproliferation of astrocytes, which in turn induced excessive vasculogenesis. Thus, PDGF appears to be a link in the chain of cell-cell interactions responsible for matching numbers of neurons, astrocytes, and blood vessels during retinal development.

Angiopoietin1/TIE2 and VEGF/FLK1 Induced by MSC Treatment Amplifies Angiogenesis and Vascular Stabilization after Stroke

“…Astrocytes are potent regulators of brain capillary endothelial cell function and have a profound influence on the morphogenetic events underlying the organization of the vessel wall (Ramsauer et al, 2002). The astrocyte network strongly affects vascular patterning (Fruttiger et al, 1996). Endothelial cells at the leading edge of the vascular plexus possess long filopodia that closely follow the underlying astrocyte scaffold (Dorrell et al, 2002;Gerhardt and Betsholtz, 2003).…”

Platelet-Derived Growth Factor-A-Induced Retinal Gliosis Protects against Ischemic Retinopathy

“…Fruttiger and associates 36 used the neuron-specific enolase (NSE) promoter to drive expression of the short isoform of PDGF-A, beginning before the day of birth in retinal ganglion cells and some cells of the inner and outer nuclear layer of transgenic mice. These mice showed numerous ectopic astrocytes that extended throughout the entire depth of the retina, but the radial spread of astrocytes from the optic nerve to the periphery was decreased.…”

Vascular endothelial growth factor in eye disease

“…Immediately prior to the development of the vascular plexus, a network of astrocytes radiates from the optic nerve head across the surface of the immature retina in a central to peripheral pattern. This network forms the scaffold upon which the primary vascular plexus is formed (Ling and Stone, 1988;Fruttiger et al,1996). Astrocytes express VEGF, which promotes endothelial cell proliferation and migration within this superficial plane (Stone et al, 1995).…”