Steinle Jena J, Cappocia Frank C, Jiang Youde
Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Growth Factors. 2008 Dec;26(6):325-30. doi: 10.1080/08977190802442070.
Remodeling of the choroidal vasculature is a prominent factor in age-related macular degeneration. While many of the growth factors involved in this vascular remodeling are known, their regulation remains much less so. The hypothesis of the present study was that stimulation of human choroidal endothelial cells with the beta-adrenergic receptor agonist isoproterenol would lead to an increase in pigment epithelial derived factor (PEDF) and angiopoietin 1 (Ang1), markers of a stable vasculature. Protein levels of PEDF and Ang1 were significantly increased following stimulation with isoproterenol. However, isoproterenol also significantly increased protein levels of vascular endothelial cell growth factor, which is active during vasculature remodeling. These data suggest that beta-adrenergic receptor agonists are likely upstream of a number of growth factors implicated in ocular disease and have multiple effects on choroidal endothelial cells. Modulation of this signaling in the choroid may offer a new avenue for therapeutics.
脉络膜血管重塑是年龄相关性黄斑变性的一个突出因素。虽然已知许多参与这种血管重塑的生长因子,但其调控机制仍知之甚少。本研究的假设是,用β-肾上腺素能受体激动剂异丙肾上腺素刺激人脉络膜内皮细胞会导致色素上皮衍生因子(PEDF)和血管生成素1(Ang1)增加,这两种因子是稳定血管系统的标志物。用异丙肾上腺素刺激后,PEDF和Ang1的蛋白水平显著增加。然而,异丙肾上腺素也显著增加了血管内皮细胞生长因子的蛋白水平,该因子在血管重塑过程中具有活性。这些数据表明,β-肾上腺素能受体激动剂可能是许多与眼部疾病相关的生长因子的上游因子,并且对脉络膜内皮细胞有多种作用。调节脉络膜中的这种信号传导可能为治疗提供一条新途径。