ASTROCYTES MODULATE RETINAL VASCULOGENESIS - EFFECTS ON ENDOTHELIAL-CELL DIFFERENTIATION

In the developing retina, the microvessels form by differentiation of endothelial precursor cells in a process referred to as vasculogenesis . Experiments using in vivo and in vitro model systems were designed t o determine the specific influence of astrocytes on this process. Immu nolocalization analyses of retinal vasculogenesis in vivo showed that astrocytes spread within the nerve fiber layer of the neonatal rat ret ina just ahead of the forming vessels. Then, endothelial precursor cel ls align themselves in register with the astrocytes. In contact with a strocytes, precursor cells differentiate as vascular endothelium, as i ndicated by lumen formation and patency to red blood cells. Experiment s in vitro using cell culture and conditioned medium approaches showed that cell-cell contact between rat brain astrocytes and bovine retina l endothelial cells results in release of soluble factors, inhibiting endothelial cell growth and inducing morphological differentiation in capillary-like structures. Thus, it is suggested that astrocytes lay d own the pattern for vasculogenesis and induce the elongation and align ment of endothelial precursor cells into a prevascular meshwork. In co ntact with astrocytes, precursor cells differentiate as vascular endot helium. Furthermore, this cell-cell contact with astrocytes apparently inhibits endothelial cell growth and stimulates their elongation, ali gnment, and morphogenic differentiation by means of the release or act ivation of soluble, growth factor-like substances. (C) 1995 Wiley-Liss , Inc.