Ascorbic acid (AsA) is highly concentrated in vitreous in bovine, human as well as in other species. In order to evaluate the role of ascorbic acid as an ocular neovascularization inhibitor, we examined the effect of ascorbic acid on growth and survival of cultured vascular endothelial cells. When added to culture medium, high concentration of ascorbic acid (0.3 mM<) reduced viability of bovine aortic endothelial cells (BAEC) within 24 hr. Morphology of ascorbic acid treated endothelial cells demonstrated that fragmentation of nuclei does not accompany during this incubation period, suggesting that ascorbic acid induces vascular endothelial cell death in a non-apoptotic manner. To further confirm that this event was not specific on BAEC, bovine retinal endothelial cells (BREC) and human aortic endothelial cells (HAEC) were tested for ascorbic acid cytotoxicity. Ascorbic acid induced cell death in all three types of cells, but the dose required for induction of cell death differed, human endothelial cells were apparently more resistant to ascorbic acid cytotoxicity than bovine cells. Decrease in viability of BAEC exposed to ascorbic acid were partially inhibited by exposure to low oxygen concentration (O2 = 1%). Addition of vascular endothelial growth factor (VEGF) stimulated proliferation of both BAEC and BREC, but co-addition of ascorbic acid reduced VEGF-induced endothelial cell proliferation. These results show that ascorbic acid modulates endothelial cell behavior in vitro and suggest that it is a negative regulator for ocular neovascularization.
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