VEGF mRNA and Protein Concentrations in the Developing Human Eye

BACKGROUND: Vascular endothelial growth factor (VEGF), a well-characterized regulator of angiogenesis, has been mechanistically implicated in retinal neovascularization and in the pathogenesis of ROP. However, the ontogeny of VEGF expression in the human fetal retina is not well known. Because retinal vasculature grows with gestational maturation, we hypothesized that VEGF expression also increases in the midgestation human fetal eye as a function of gestational age. METHODS: To identify changes in VEGF gene expression during normal human development, we measured VEGF mRNA by quantitative PCR and measured VEGF protein by ELISA and western blots in 10-24 week gestation fetal vitreous, retina, and serum. RESULTS: VEGF mRNA expression in the retina increased with gestational age. VEGF isoform A, particularly its VEGF(121) splice variant, contributed to this positive correlation. Consistent with these findings, we detected increasing VEGF(121) protein concentrations in vitreous humor from fetuses of 10-24 weeks gestation, while VEGF concentrations decreased in fetal serum. CONCLUSIONS: VEGF(121) mRNA and protein concentrations increase with increasing gestational age in the developing human retina. We speculate that VEGF plays an important role in normal retinal vascular development, and that preterm delivery affects production of this vascular growth factor.