Robo4因具有调节血管通透性、促进新生血管形成等作用而在糖尿病视网膜病变（DR）的研究中日益受到重视。已有研究显示，Robo4可影响DR的发生与发展，但其对视网膜微血管改变的作用及机制尚不清楚。在Robo4表达调控机制的研究中，我们发现HIF-1α可通过某种途径正向调节Robo4的表达，且预测分析显示SP1与HIF-1α、Robo4均可能存在调控关系。由此推测：HIF-1α通过激活SP1实现对Robo4的调控，从而加重视网膜微血管的异常改变，促进DR的发生发展。本研究拟采用不同种类的视网膜细胞深入探讨HIF-1α、SP1、Robo4三者间的调控关系和机制，并于动物模型中检测在DR发生发展过程中三者间调控机制是否存在，及该机制对视网膜微血管结构和功能的影响。本课题旨在进一步拓展对糖尿病视网膜病变发病分子机制的认识，为早期干预DR提供新的理论依据和研究方向。

Robo4 attracts great attentions in the research of diabetic retinopathy (DR), due to its function on vascular permeability and neovascularization. Recent studies show that Robo4 could facilitate the occurrence and development of DR, but its role in retinal microvascular abnormalities and the relative mechanisms are still unknown. In the previous research, we found for the first time that HIF-1α could up-regulate the expression of Robo4 through an indirect way, and PROMOTER 2.0 software also predicts SP1 exists regulatory relationships with HIF-1α and Robo4 respectively. Therefore, we put forward the hypothesis that HIF-1α can activate SP1 to regulate the expression of Robo4, which aggravates the dysfunction of retinal vessels and then promotes the progress of DR. On the basis of previous work, we will use human retinal endothelial cells and retinal pigment epithelium cells to investigate the exact regulation mechanism among HIF-1α、SP1 and Robo4, which will also be verified in the diabetic animal model. Furthermore, the influence of HIF-1α、SP1 and Robo4 on functional changes in retinal vessel is explored during the occurrence and development of DR. These studies would give useful evidences to reveal a new molecular pathogenesis of retinal vascular dysfunction in DR, as well as providing the profound basis and therapeutic way for early DR intervention.