Department of Ophthalmology, College of Medicine, Seoul National University & Seoul Artificial Eye Center Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Vascul Pharmacol. 2009 Oct;51(4):262-7. doi: 10.1016/j.vph.2009.06.010. Epub 2009 Jul 6.
Pathological angiogenesis is the most common cause of vision loss at all ages including retinopathy of prematurity (ROP), diabetic retinopathy, and age-related macular degeneration. ROP is a proliferative disease of the retinal vasculature in premature infants. Herein, we demonstrated caffeic acid (CA) has the anti-angiogenic activity to retinal endothelial cells and retinal neovascularization in a mouse model of ROP, which might be related to the suppression of ROS-induced VEGF expression. CA effectively inhibited VEGF-induced proliferation of retinal endothelial cells in concentration-dependent manner. In addition, VEGF-induced migration and tube formation of retinal endothelial cells were completely inhibited. This anti-angiogenic activity of CA on retinal endothelial cells was related to the anti-oxidant activity: the inhibitory activity of CA to H(2)O(2)-induced reactive oxygen species production and VEGF expression. Interestingly, CA significantly suppressed retinal neovascularization in oxygen-induced retinopathy as the animal model of ROP without retinal cytotoxicity. These data suggests that CA could be a potent anti-angiogenic agent for retinal neovascularization, and be applied in the treatment of other vaso-proliferative retinopathies.
病理性血管生成是导致所有年龄段视力丧失的最常见原因，包括早产儿视网膜病变（ROP）、糖尿病性视网膜病变和年龄相关性黄斑变性。ROP 是早产儿视网膜血管的增殖性疾病。在此，我们证明了咖啡酸（CA）具有抗血管生成活性，可以抑制视网膜血管内皮细胞和 ROP 小鼠模型中的视网膜新生血管形成，这可能与抑制 ROS 诱导的 VEGF 表达有关。CA 能够以浓度依赖的方式有效抑制 VEGF 诱导的视网膜内皮细胞增殖。此外，CA 还完全抑制了 VEGF 诱导的视网膜内皮细胞迁移和管腔形成。CA 对视网膜内皮细胞的这种抗血管生成活性与抗氧化活性有关：CA 抑制 H(2)O(2)诱导的活性氧产生和 VEGF 表达。有趣的是，CA 可显著抑制氧诱导的视网膜病变中的视网膜新生血管形成，而对视网膜无细胞毒性。这些数据表明，CA 可能是一种有效的抗视网膜新生血管形成的药物，可应用于治疗其他血管增殖性视网膜病变。
