VASCULAR ENDOTHELIAL GROWTH-FACTOR ACTS AS A SURVIVAL FACTOR FOR NEWLY FORMED RETINAL-VESSELS AND HAS IMPLICATIONS FOR RETINOPATHY OF PREMATURITY

Retinopathy of prematurity (ROP) is initiated by hyperoxia-induced obl iteration of newly formed blood vessels in the retina of the premature newborn. We propose that vessel regression is a consequence of hypero xia-induced withdrawal of a critical vascular survival factor. We show that regression of retinal capillaries in neonatal rats exposed to hi gh oxygen, is preceded by a shut-off of vascular endothelial growth fa ctor (VEGF) production by nearby neuroglial cells. Vessel regression o ccurs via selective apoptosis of endothelial cells. Intraocular inject ion of VEGF at the onset of experimental hyperoxia prevents apoptotic death of endothelial cells and rescues the retinal vasculature. These findings provide evidence for a specific angiogenic factor acting as a vascular survival factor in vivo. The system also provides a paradigm for vascular remodelling as an adaptive response to an increase in ox ygen tension and suggests a novel approach to prevention of ROP.