Notch and TGF-beta in the Control of Retinal Vascular Integrity

摘要 糖尿病视网膜病变是糖尿病最常见的并发症之一。基底膜增厚 和周细胞损失是与糖尿病视网膜病变的发展相关的早期变化。我推测 这些事件破坏了Notch信号传导，该信号传导依赖于细胞膜的并置， Notch和TGF-β信号传导之间的细胞信号传导串扰。为了验证这一假设，我建议：（一）建立 使用成像方法测量由Notch介导的细胞-细胞相互作用的细胞培养系统;（ii）检查 在类似糖尿病的条件下培养的血管细胞中Notch/TGF-β信号传导如何受到影响 环境;和，（iii）使用小鼠模型和死后人眼组织来检查 Notch/TGF-β在糖尿病视网膜病变中的相互作用我提出一个训练计划， 拟议的实验和向职业独立过渡的战略。

ABSTRACT Diabetic retinopathy is among the most common complications of diabetes. Basement membrane thickening and pericyte loss are early changes associated with the development of diabetic retinopathy. I speculate that these events disrupt Notch signaling, which depends upon juxtaposition of cellular membranes, and also impair cell signaling cross-talk between Notch and TGF-¿ signaling. To test this hypothesis, I propose to: (i) establish a cell culture system to measure cell-cell interactions mediated by Notch using imaging methods; (ii) examine how Notch/TGF-¿ signaling is affected in vascular cells cultured under conditions resembling a diabetic environment; and, (iii) use mouse models and postmortem human eye tissue for examining the role of Notch/TGF- ¿ interactions in diabetic retinopathy. I propose a training plan that will enable me to accomplish the proposed experiments and a strategy for transition towards career independence.