Zhang Hui-Ying, Zhang Qiu-Yang, Liu Qing, Feng Si-Guo, Ma Yan, Wang Feng-Sheng, Zhu Yue, Yao Jin, Yan Biao
The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, 210000, China.
The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, 210000, China.
J Nanobiotechnology. 2025 Jan 22;23(1):36. doi: 10.1186/s12951-024-03079-y.
Pathological neovascularization is a hallmark of many vision-threatening diseases. However, some patients exhibit poor responses to current anti-VEGF therapies due to resistance and limited efficacy. Recent studies have highlighted the roles of noncoding RNAs in various biological processes, paving the way for RNA-based therapeutics. In this study, we report a marked down-regulation of miR-205 under pathological conditions. miR-205 potently inhibits endothelial cell functions critical for pathological neovascularization, including proliferation, migration, and tube formation. Furthermore, miR-205 strengthens the endothelial barrier, thereby reducing vascular leakage. In mouse models of retinal and choroidal neovascularization, miR-205 administration effectively suppresses abnormal blood vessel formation and leakage. Mechanistically, miR-205 directly targets VEGFA and ANGPT2, which are key drivers of pathological neovascularization. To improve delivery, we successfully loaded miR-205 into exosomes derived from mesenchymal stem cells. This innovative approach avoids cytotoxicity while preserving therapeutic efficacy in both cellular and animal models. Collectively, our findings highlight miR-205 as a promising therapeutic for ocular neovascularization, with exosome delivery offering a novel and efficient strategy for treating vision-threatening vascular diseases.
病理性血管生成是许多威胁视力疾病的一个标志。然而，由于耐药性和疗效有限，一些患者对当前的抗血管内皮生长因子（VEGF）疗法反应不佳。最近的研究突出了非编码RNA在各种生物学过程中的作用，为基于RNA的治疗方法铺平了道路。在本研究中，我们报告了在病理条件下miR-205显著下调。miR-205有力地抑制了对病理性血管生成至关重要的内皮细胞功能，包括增殖、迁移和管腔形成。此外，miR-205增强了内皮屏障，从而减少血管渗漏。在视网膜和脉络膜新生血管的小鼠模型中，给予miR-205可有效抑制异常血管形成和渗漏。从机制上讲，miR-205直接靶向VEGFA和ANGPT2，它们是病理性血管生成的关键驱动因素。为了改善递送，我们成功地将miR-205装载到源自间充质干细胞的外泌体中。这种创新方法在细胞和动物模型中避免了细胞毒性，同时保留了治疗效果。总体而言，我们的研究结果突出了miR-205作为一种有前景的眼部新生血管治疗方法，外泌体递送为治疗威胁视力的血管疾病提供了一种新颖且有效的策略。
