산화스트레스하의 망막색소상피세포에서 VEGF 증가와 PEDF의 감소에 의한 혈관신생

Abstract

This study is to aim to elucidate the mechanism of neoangiogenesis in human retinal pigment epithelium under oxidative stress. Paraquat was added to cultured human retinal pigment epithelium (HRPE) for 72 hr to induce oxidative stress milieu. Expression and production of angiogenic factors including vascular endothelial growth factor (VEGF) and pigment endothelial derived factor (PEDF) was checked by RT-PCR and Western blot, respectively. Whether or not induction of the neoangiogenesis was monitored by both tube formation in ECV 304 cell and migration assay of human fetal dermal microvascular endothelial cells. The competitive RT-PCR showed that PEDF gene in paraquat-treated RPE was significantly lower expressed than in non-treated HRPE. But Western blot showed the significant increase of VEGF production (p＜0.05) and the decrease of PEDF production (p＜0.05). Moreover, angiogenesis was dose-dependently increased when the various concentrations of paraquat were added to HRPE. Taken together, oxidative stress by addition of paraquat causes HRPE to produce VEGF more and PEDF less, leading to neoangiogenesis, suggesting that the neovasculization in age-related macular degeneration (AMD) be caused by breaking the balance of angiogenic factors in HRPE such as VEGF and PEDF-that is, in oxidative stressed HRPE, VEGF releases higher and PEDF lower, as compared to the normal HRPE.