Retinal vascular endothelial growth factor (VEGF) mRNA expression is altered in relation to neovascularization in oxygen induced retinopathy.

Abstract

The temporal and spatial expression of vascular endothelial cell growth factor (VEGF) mRNA was studied in normal developing cat retina, and in oxygen induced retinopathy. Unexposed control and oxygen-exposed animals (80 h of 80% oxygen from day 3, n = 16) were studied at 1, 2, 4, and 6 weeks after birth. India ink injected retinal flat mounts were used to study vessel progression, and in situ hybridizations using retinal cross sections were used to assess VEGF mRNA accumulation. In controls, as the retina matured, VEGF mRNA hybridization was evident in the ganglion cell layer in a scattered line of distinct cells prior to the ingrowth of vessels, involved the most cells in regions just peripheral to invading vessels and persisted in a fewer positive cells, widely spaced in the vascularized retinas of control, six week animals. In the inner nuclear layer, hybridization initially appeared diffusely and later became localized to a narrow portion of that layer and persisted there. In animals with oxygen induced retinopathy, a substantial increase in hybridization was observed in both the ganglion cell and inner nuclear layers of the avascular retina anterior to the advancing neovascularization. VEGF hybridization decreased abruptly to background levels in both layers at the point were neovascularization met avascular retina. By six weeks, when the neovascularization reached the ora, there was a return of VEGF mRNA in the inner nuclear layer which was similar to normal control expression. A low level of unchanging expression was also observed in the retinal pigment epithelium in both groups at all ages. These results indicate that VEGF mRNA abundance is regulated during retinal vascularization and is increased in relation to oxygen induced neovascularization, suggesting that VEGF may play an important role in both normal retinal vessel development and in the pathophysiology of retinopathy of prematurity.