4217 Constitutive expression of the VEGF receptor KDR/FLK-1 in corneal endothelial cell mediates their proliferation

Purpose. Vascular endothelial growth factor (VEGF) binds to oorneal endothelial cells (BCE). We screened BCE for the expression of the VEGF receptors KDRIFLK-I and FLT-1 and analysed their functions. Methods. The expression of KDRIFLK-1 and FLT-1 mRNA was analysed by northern-blot. BCE were also transfeoted with expression vectors carriing the VEGF receptors sequences. Their ability to proliferate upon VEGF or specific KDR ligands was studied. Results. BCE cells express FLT-1, migrate but do not proliferate upon VEGF addition. Constitutive expression of KDWFLK-I confers to BCE cells the ability to proliferate in response to VEGF. Moreover the oligomerization of KDR/FLK-1 obtained by bivalent ligands leads to higher mitogenic response than that obtained with VEGF, whereas monovalent ligand have no effect. Conclusion. These results emphasize the requirement of KDR/FLK-1 oligomerization for BCE proliferation.