RETINAL VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) MESSENGER-RNA EXPRESSION IS ALTERED IN RELATION TO NEOVASCULARIZATION IN OXYGEN-INDUCED RETINOPATHY

The temporal and spatial expression of vascular endothelial cell growt h factor (VEGF) mRNA was studied in normal developing cat retina, and in oxygen induced retinopathy. Unexposed control and oxygen-exposed an imals (80 h of 80% oxygen from day 3, n = 16) were studied at 1, 2, 3, and 6 weeks after birth. India ink injected retinal flat mounts were used to study vessel progression, and in situ hybridizations using ret inal cross sections were used to assess VEGF mRNA accumulation. In con trols, as the retina matured, VEGF mRNA hybridization was evident in t he ganglion cell layer in a scattered line of distinct cells prior to the ingrowth of vessels, involved the most cells in regions just perip heral to invading vessels and persisted in a fewer positive cells, wid ely spaced in the vascularized retinas of control, six week animals. I n the inner nuclear layer, hybridization initially appeared diffusely and later became localized to a narrow portion of that layer and persi sted there. In animals with oxygen induced retinopathy, a substantial increase in hybridization was observed in both the ganglion cell and i nner nuclear layers of the avascular retina anterior to the advancing neovascularization. VEGF hybridization decreased abruptly to backgroun d levels in both layers at the point were neovascularization met avasc ular retina. By six weeks, when the neovascularization reached the era , there was a return of VEGF mRNA in the inner nuclear layer which was similar to normal control expression. A low level of unchanging expre ssion was also observed in the retinal pigment epithelium in both grou ps at all ages. These results indicate that VEGF mRNA abundance is reg ulated during retinal vascularization and is increased in relation to oxygen induced neovascularization, suggesting that VEGF may play an im portant role in both normal retinal vessel development and in the path ophysiology of retinopathy of prematurity.