Angiogenesis is required for tissue repair; but abnormal angiogenesis or neovascularization (NV) causes diseases in the eye. The avascular status in the cornea is a prerequisite for corneal clarity and thought to be maintained by the equilibrium between proangiogenic and antiangiogenic factors that controls proliferation and migration of vascular endothelial cells (ECs) sprouting from the pericorneal plexus. VEGF is the most important intrinsic factor for angiogenesis; anti-VEGF therapies are available for treating ocular NV. However, the effectiveness of the therapies is limited because of VEGF-independent mechanism(s). We show that Zeb1 is an important factor promoting vascular EC proliferation and corneal NV; and a couple of small molecule inhibitors can evict Ctbp from the Zeb1–Ctbp complex, thereby reducing EC Zeb1 expression, proliferation, and corneal NV. We conclude that Zeb1-regulation of angiogenesis is independent of Vegf and that the ZEB1–CtBP inhibitors can be of potential therapeutic significance in treating corneal NV.

组织修复需要血管生成；但异常的血管生成或新生血管形成 (NV) 会导致眼部疾病。角膜中的无血管状态是角膜清晰度的先决条件，并且被认为是通过促血管生成因子和抗血管生成因子之间的平衡来维持的，这些因子控制从角膜周围神经丛萌发的血管内皮细胞（EC）的增殖和迁移。 VEGF是血管生成最重要的内在因子；抗 VEGF 疗法可用于治疗眼部 NV。然而，由于 VEGF 独立机制，治疗的有效性受到限制。我们证明Zeb1是促进血管EC增殖和角膜NV的重要因子；一些小分子抑制剂可以将 Ctbp 从 Zeb1-Ctbp 复合物中驱逐，从而减少 EC Zeb1 表达、增殖和角膜 NV。我们得出的结论是，Zeb1 对血管生成的调节独立于 Vegf，并且 ZEB1-CtBP 抑制剂在治疗角膜 NV 方面具有潜在的治疗意义。