Huang Qiong, Sheibani Nader
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792-4673, USA.
Am J Physiol Cell Physiol. 2008 Dec;295(6):C1647-57. doi: 10.1152/ajpcell.00322.2008. Epub 2008 Oct 22.
Hyperglycemia impacts retinal vascular function and promotes the development and progression of diabetic retinopathy, which ultimately results in growth of new blood vessels and loss of vision. How high glucose affects retinal endothelial cell (EC) properties requires further investigation. Here we determined the impact of high glucose on mouse retinal EC function in vitro. High glucose significantly enhanced the migration of retinal EC without impacting their proliferation, apoptosis, adhesion, and capillary morphogenesis. The enhanced migration of retinal EC under high glucose was reversed in the presence of the antioxidant N-acetylcysteine, suggesting increased oxidative stress under high-glucose conditions. Retinal EC under high-glucose conditions also expressed increased levels of fibronectin, osteopontin, and alpha(v)beta(3)-integrin, and reduced levels of thrombospondin-1. These changes were concomitant with sustained activation of the downstream prosurvival and promigratory signaling pathways, including Src kinase, phosphatidylinositol 3-kinase/Akt1/endothelial nitric oxide synthase, and ERKs. The sustained activation of these signaling pathways was essential for enhanced migration of retinal EC under high-glucose conditions. Together, our results indicate the exposure of retinal EC to high glucose promotes a promigratory phenotype. Thus alterations in the proangiogenic properties of retinal EC during diabetes may contribute to the development and pathogenesis of diabetic retinopathy.
高血糖会影响视网膜血管功能，并促进糖尿病视网膜病变的发生和发展，最终导致新生血管生长和视力丧失。高糖如何影响视网膜内皮细胞（EC）的特性仍需进一步研究。在此，我们在体外确定了高糖对小鼠视网膜EC功能的影响。高糖显著增强了视网膜EC的迁移能力，而不影响其增殖、凋亡、黏附及毛细血管形态发生。在抗氧化剂N-乙酰半胱氨酸存在的情况下，高糖条件下视网膜EC增强的迁移能力被逆转，这表明在高糖条件下氧化应激增加。高糖条件下的视网膜EC还表现出纤连蛋白、骨桥蛋白和α(v)β(3)-整合素水平升高，而血小板反应蛋白-1水平降低。这些变化与下游促生存和促迁移信号通路的持续激活相伴，包括Src激酶、磷脂酰肌醇3激酶/Akt1/内皮型一氧化氮合酶和细胞外信号调节激酶。这些信号通路的持续激活对于高糖条件下视网膜EC迁移增强至关重要。总之，我们的结果表明视网膜EC暴露于高糖环境会促进促迁移表型。因此，糖尿病期间视网膜EC促血管生成特性的改变可能有助于糖尿病视网膜病变的发生和发病机制。
