Exosome-loading miR-205: a two-pronged approach to ocular neovascularization therapy
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-024-03079-y |
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| author | Hui-ying Zhang Qiu-yang Zhang Qing Liu Si-guo Feng Yan Ma Feng-sheng Wang Yue Zhu Jin Yao Biao Yan |
| author_facet | Hui-ying Zhang Qiu-yang Zhang Qing Liu Si-guo Feng Yan Ma Feng-sheng Wang Yue Zhu Jin Yao Biao Yan |
| author_sort | Hui-ying Zhang |
| collection | DOAJ |
| description | Abstract 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. Graphical Abstract |
| format | Article |
| id | doaj-art-ce1621e774194613889ee8bb393076eb |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-ce1621e774194613889ee8bb393076eb2025-01-26T12:50:55ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123112010.1186/s12951-024-03079-yExosome-loading miR-205: a two-pronged approach to ocular neovascularization therapyHui-ying Zhang0Qiu-yang Zhang1Qing Liu2Si-guo Feng3Yan Ma4Feng-sheng Wang5Yue Zhu6Jin Yao7Biao Yan8The Affiliated Eye Hospital, Nanjing Medical UniversityThe Affiliated Eye Hospital, Nanjing Medical UniversityThe Affiliated Eye Hospital, Nanjing Medical UniversityThe Affiliated Eye Hospital, Nanjing Medical UniversityThe Affiliated Eye Hospital, Nanjing Medical UniversityThe Affiliated Eye Hospital, Nanjing Medical UniversityThe Affiliated Eye Hospital, Nanjing Medical UniversityThe Affiliated Eye Hospital, Nanjing Medical UniversityDepartment of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract 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. Graphical Abstracthttps://doi.org/10.1186/s12951-024-03079-yOcular neovascularizationmiR-205VEGFAANGPT2Exosomes |
| spellingShingle | Hui-ying Zhang Qiu-yang Zhang Qing Liu Si-guo Feng Yan Ma Feng-sheng Wang Yue Zhu Jin Yao Biao Yan Exosome-loading miR-205: a two-pronged approach to ocular neovascularization therapy Journal of Nanobiotechnology Ocular neovascularization miR-205 VEGFA ANGPT2 Exosomes |
| title | Exosome-loading miR-205: a two-pronged approach to ocular neovascularization therapy |
| title_full | Exosome-loading miR-205: a two-pronged approach to ocular neovascularization therapy |
| title_fullStr | Exosome-loading miR-205: a two-pronged approach to ocular neovascularization therapy |
| title_full_unstemmed | Exosome-loading miR-205: a two-pronged approach to ocular neovascularization therapy |
| title_short | Exosome-loading miR-205: a two-pronged approach to ocular neovascularization therapy |
| title_sort | exosome loading mir 205 a two pronged approach to ocular neovascularization therapy |
| topic | Ocular neovascularization miR-205 VEGFA ANGPT2 Exosomes |
| url | https://doi.org/10.1186/s12951-024-03079-y |
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