Retinoic acid induces VEGF gene expression in human retinal pigment epithelial cells (ARPE-19)

Purpose: The aim of this study was to evaluate the expression of vascular endothelial growth factor (VEGF) in response to retinoic acid (RA) in human retinal pigment epithelial cells. Methods: Expression of VEGF in human ARPE-19 cells was determined by a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). mRNA stability was assessed after the administration of actinomycin D. The induction of the VEGF gene by various RAS was also determined by semiquantitative RT-PCR. Results: All-trans retinoic acid (atRA) time-dependently increased VEGF mRNA levels. The effect of atRA was dose-dependent in a range between 10(-7) M and 10(-6) M. Treatment with actinomycin D revealed that atRA induces the VEGF gene at the transcriptional level. Of the various RAS tested, atRA was the most potent inducer of the VEGF gene. Conclusions: We demonstrated that atRA stimulates the induction of the VEGF gene in ARPE-19 cells, suggesting a novel pathway for the development of age-related macular degeneration.