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 周细胞丢失是与糖尿病视网膜病变发展相关的早期改变。我推测 这些事件扰乱了依赖于细胞膜并列的Notch信号，也损害了 细胞信号在Notch和转化生长因子-B信号之间的串扰。为了检验这一假设，我建议：(I)建立 使用成像方法测量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/转化生长因子-B信号是如何受到影响的 以及，(Iii)使用小鼠模型和死后人眼组织来研究 糖尿病视网膜病变中Notch/转化生长因子-β的相互作用。我提出了一项培训计划，使我能够完成 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-ß 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-ß 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-ß 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.