Scholarlink

<p>Retinal neovascularization (RNV) is a leading cause of blindness. Although anti-VEGF therapy remains the first-line treatment for RNV, a subset of patients exhibits poor or no response to anti-VEGF agents. Therefore, exploring alternative therapeutic strategies is imperative. Rac1, a small GTPase, has been reported to regulate angiogenesis through multiple signaling pathways. Nevertheless, the precise role of Rac1 in RNV progression remains unclear. Our study demonstrates that NSC23766, a Rac1 activation inhibitor, effectively attenuates VEGF-induced angiogenic responses in human retinal microvascular endothelial cells (HRMECs), including proliferation, migration, invasion, and tube formation. Furthermore, phalloidin staining revealed that NSC23766 significantly inhibits VEGF-induced cytoskeleton rearrangement in HRMECs while modulating phosphorylation levels of LIMK and cofilin. Western blot analysis reveals that VEGF-induced VEGFR2 phosphorylation activates Rac1 in a time-dependent manner. Further investigation demonstrates that NSC23766 suppresses VEGFR2 phosphorylation by blocking Rac1 activation. Based on these findings, we propose the existence of a positive feedback loop between Rac1 and VEGFR2. Notably, in an oxygen-induced retinopathy (OIR) mouse model, intravitreal injection of NSC23766 significantly attenuated RNV progression. Therefore, our findings suggest that NSC23766 is a potential therapeutic strategy for RNV by disrupting the positive feedback loop between Rac1 and VEGFR2.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

NSC23766 effectively inhibited retinal neovascularization by disrupting the positive feedback loop between Rac1 and VEGFR2

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月20日

查看全文
  • Jisen Tang,
  • Duo Li,
  • Gukun Yang,
  • Huanshen Li,
  • Weihong Li,
  • Yuanwei Li,
  • Yikeng Huang,
  • Xionggao Huang

摘要

Retinal neovascularization (RNV) is a leading cause of blindness. Although anti-VEGF therapy remains the first-line treatment for RNV, a subset of patients exhibits poor or no response to anti-VEGF agents. Therefore, exploring alternative therapeutic strategies is imperative. Rac1, a small GTPase, has been reported to regulate angiogenesis through multiple signaling pathways. Nevertheless, the precise role of Rac1 in RNV progression remains unclear. Our study demonstrates that NSC23766, a Rac1 activation inhibitor, effectively attenuates VEGF-induced angiogenic responses in human retinal microvascular endothelial cells (HRMECs), including proliferation, migration, invasion, and tube formation. Furthermore, phalloidin staining revealed that NSC23766 significantly inhibits VEGF-induced cytoskeleton rearrangement in HRMECs while modulating phosphorylation levels of LIMK and cofilin. Western blot analysis reveals that VEGF-induced VEGFR2 phosphorylation activates Rac1 in a time-dependent manner. Further investigation demonstrates that NSC23766 suppresses VEGFR2 phosphorylation by blocking Rac1 activation. Based on these findings, we propose the existence of a positive feedback loop between Rac1 and VEGFR2. Notably, in an oxygen-induced retinopathy (OIR) mouse model, intravitreal injection of NSC23766 significantly attenuated RNV progression. Therefore, our findings suggest that NSC23766 is a potential therapeutic strategy for RNV by disrupting the positive feedback loop between Rac1 and VEGFR2.