Resveratrol Suppresses Expression of VEGF by Human Retinal Pigment Epithelial Cells: Potential Nutraceutical for Age-related Macular Degeneration
Resveratrol Suppresses Expression of VEGF by Human Retinal Pigment Epithelial Cells: Potential Nutraceutical for Age-related Macular Degeneration
复制标题
DOI：
10.14366/ad.2014.050088
复制
发表时间：
2014-04-01
影响因子：
7.4
通讯作者：
Detrick, Barbara
中科院分区：
文献类型：
--
作者：
Nagineni, Chandrasekharam N.;Raju, Raghavan;Detrick, Barbara
年龄相关性黄斑变性 (AMD) 是一种威胁视力的视网膜眼病，影响着全球数百万老年人。眼睛后室的脉络膜-视网膜色素上皮 (RPE)-神经视网膜轴是 AMD 病理的主要部位。有令人信服的证据表明血管内皮生长因子 (VEGF) 与 AMD 相关。在此，我们报道了白藜芦醇 (RSV) 对炎症细胞因子、TGF-β 和缺氧诱导的人视网膜色素上皮细胞 (HRPE) 分泌 VEGF 的抑制作用。本报告的研究使用了从老年人类供体眼睛制备的 HRPE 培养物。 HRPE 持续分泌少量 VEGF-A 和 VEGF-C。用炎症细胞因子混合物（IFN-γ、TNF-α、IL-1β）刺激可显着增加 VEGF-A 和 VEGF-C 的分泌。 RSV以剂量依赖性（10-50 uM）方式显着抑制炎症细胞因子诱导的VEGF-A和VEGF-C分泌。 RT-PCR 分析表明，RSV 对 VEGF 分泌的影响可能是由于 mRNA 水平降低所致。转化生长因子-β。氯化钴（模拟缺氧）也上调 HRPE 细胞 VEGF-A 的产生，而这一作用被 RSV 抑制。相反，RSV对抗血管生成分子、内皮抑素和色素上皮衍生因子的分泌没有影响。使用体外划痕试验的研究表明，RSV 也会抑制伤口闭合。这些结果表明RSV可以抑制炎症细胞因子、TGF-β和缺氧诱导的VEGF分泌。在病理条件下，VEGF 的过度表达已知会使 AMD 恶化。因此，RSV 可作为营养保健品来控制 AMD 的病理性脉络膜新生血管形成过程。
Age-related macular degeneration (AMD) is a sight threating retinal eye disease that affects millions of aging individuals world-wide. Choroid-retinal pigment epithelium (RPE)-neuroretina axis in the posterior compartment of the eye is the primary site of AMD pathology. There are compelling evidence to indicate association of vascular endothelial growth factors (VEGF) to AMD. Here, we report the inhibitory actions of resveratrol (RSV) on inflammatory cytokine, TGF-beta and hypoxia induced VEGF secretion by human retinal pigment epithelial cells (HRPE). HRPE cultures prepared from aged human donor eyes were used for the studies in this report. HRPE secreted both VEGF-A and VEGF-C in small quantities constitutively. Stimulation with a mixture of inflammatory cytokines (IFN-gamma, TNF-alpha, IL-1 beta), significantly increased the secretion of both VEGF-A and VEGF-C. RSV, in a dose dependent (10-50 uM) manner, suppressed VEGF-A and VEGF-C secretion induced by inflammatory cytokines significantly. RT-PCR analysis indicated that effects of RSV on VEGF secretion were possibly due to decreased mRNA levels. TGF-beta. and cobalt chloride (hypoxia mimic) also upregulated HRPE cell production of VEGF-A, and this was inhibited by RSV. In contrast, RSV had no effect on anti-angiogenic molecules, endostatin and pigment epithelial derived factor secretion. Studies using an in vitro scratch assay revealed that wound closure was also inhibited by RSV. These results demonstrate that RSV can suppress VEGF secretion induced by inflammatory cytokines, TGF-beta and hypoxia. Under pathological conditions, over expression of VEGF is known to worsen AMD. Therefore, RSV may be useful as nutraceutical in controlling pathological choroidal neovascularization processes in AMD.