Anti-angiogenic signaling molecules in retinal cells

血管生成，即从预先存在的血管形成新血管，是许多眼部疾病的标志，例如年龄相关性黄斑变性、增殖性糖尿病视网膜病变、早产儿视网膜病变和血管性青光眼，这些疾病是美国和全世界视力丧失的主要原因之一。血管内皮生长因子（VEGF）是血管生成的主要刺激因子，通过结合并激活两种内皮受体即VEGFR-1/FLK-1和VEGFR-2/FLT-1来发挥其作用。尽管已经证明VEGFR-2的活化是诱导血管生成的必要条件，但VEGFR-1在血管生成中的作用在很大程度上是未知的。我们将研究负责VEGFR-1的作用的分子机制，例如信号分子的激活或诱导可能驱动其在内皮细胞中的抗血管生成作用的立即早期基因（IEG）。从拟议的研究中获得的结果的意义在于它们有可能提供关于VEGFR-1如何通信以控制/抑制内皮细胞中血管生成的基本信息。血管生成在眼部疾病中的重要性是公认的。我们的长期目标是开始将从该项目获得的信息应用于临床环境中调节血管生成的策略的设计。

Angiogenesis, formation of new blood vessels from pre-existing vessels is a hallmark of many eye diseases such as age-related macular degeneration, proliferative diabetic retinopathy, retinopathy of prematurity and vascular glaucoma, which are among leading cause of visual loss in the USA and throughout the world. Vascular endothelial growth factor (VEGF), the major stimulator of angiogenesis, elicits its effect by binding to and activating two endothelial receptors namely VEGFR-1/FLK-1 and VEGFR-2/FLT-1. Although activation of VEGFR-2 has been demonstrated to be an essential requirement for induction of angiogenesis, the role of VEGFR-1 in angiogenesis is largely unknown. We will investigate the molecular mechanisms responsible for action of VEGFR-1, such as activation of signaling molecules or induction of immediate early genes (IEG) that might drive its anti-angiogenesis effects in endothelial cells. The significance of the results obtained from the proposed study lies in their potential to provide fundamental information on how VEGFR-1 communicates to control/restrain angiogenesis in endothelial cells. The importance of angiogenesis in ocular diseases is well recognized. our long-term goal is to begin to apply the information obtained from this project to the design of strategies to regulate angiogenesis in clinical settings.