ROLES OF VASCULAR ENDOTHELIAL GROWTH-FACTOR AND ASTROCYTE DEGENERATION IN THE GENESIS OF RETINOPATHY OF PREMATURITY

Purpose. To assess the role of vascular endothelial growth factor (VEG F) in the feline model of retinopathy of prematurity (ROP). Methods. R etinopathy of prematurity was induced in neonatal cats by raising them in an oxygen-enriched (70% to 80%) atmosphere for 4 days to suppress vessel formation and then returning them to room air for 3 to 27 days. In situ hybridization was used to detect the expression of VEGF and i ts high-affinity receptor, flk-1, in the retina of neonatal cats, and glial fibrillary acidic protein immunocytochemistry was used to assess astrocyte status. Results. The expression of VEGF in the innermost la yers of retina fell in hyperoxia and increased on return to room air. Vascular endothelial growth factor expression was transient; it was ma ximal where vessels were about to form, and it rapidly downregulated a fter vessels had formed. During the proliferative vasculopathy of ROP, VEGF expression was stronger than in the normally developing retina, and the astrocytes that normally express VEGF degenerated. After the d egeneration of astrocytes, VEGF was expressed by neurones of the gangl ion cell layer. flk-1 was expressed by intraretinal and preretinal ves sels. Supplemental oxygen therapy reduced or eliminated the overexpres sion of VEGF expression, astrocyte degeneration, and formation of prer etinal vessels. Conclusions. Regulation of VEGF by tissue oxygen media tes the inhibition of vessel growth during hyperoxia and the subsequen t proliferative vasculopathy. Degeneration of retinal astrocytes creat es conditions for the growth of preretinal vessels.