Survival Functions of the Vascular Endothelial Growth Factor (VEGF) Gene Family in the Retina

Abstract

Abstract: : Purpose: In this study, the survival functions of multiple members of the VEGF growth factor family were evaluated on retinal endothelial cells and in the developing rodent retina. Methods: In vitro, VEGF-A (VEGF₁₂₁ and VEGF₁₆₅), PlGF (PlGF-1 and PlGF-2), VEGF-C and VEGF-D were assayed for survival and proliferation functions, and for their ability to activate the Akt/PKB pathway in primary retinal endothelial cells. In vivo the developing retina was used to test the proliferative and survival functions of these factors following intraocular injection. Results: All of these factors are capable of protecting serum-starved cells from apoptosis. Moreover, while these factors gave varying degrees of positive results in classical proliferation assays that measure 5-bromo-2’-deoxyuridine (BrdU) incorporation, closer inspection at cell number revealed that an equal percentage of cells entered the cell cycle under all conditions. Furthermore, these factors were capable of inducing phosphorylation of the survival kinase Akt/PKB in retinal endothelial cells. In the developing retina increases in vascular density and survival activities were observed. Conclusions: In conclusion, it appears that increased vascular density in vivo and increased cell numbers in culture following stimulation by VEGF-family ligands is largely due to increased survival rather than increased proliferation. These data support the hypothesis that survival functions of VEGF family growth factors drives angiogenesis in the retina.

Keywords: cell death/apoptosis • retinal development