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Recent studies have revealed the diverse roles of noncoding RNAs in various biological processes and facilitated the research and development of the clinical application of numerous RNA drugs, including microRNAs. Here, we report the antiangiogenic activity of microRNA-29a (miR-29a) in three animal models of ocular neovascularization. The miR-29a knockout (KO) mice displayed enhanced vessel pruning, resulting in a decreased vascularized area during retinal development. In contrast, miR-29a deletion in adult mice accelerated angiogenesis in preclinical disease models, including corneal neovascularization, oxygen-induced retinopathy, and choroidal neovascularization, while the administration of agomir-29a ameliorated pathological neovascularization. Furthermore, miR-29a exerted inhibitory effects on endothelial cell proliferation, migration, and tube formation capacities. RNA sequencing analysis of retinas from miR-29a KO mice and RNA interference experiments identified platelet-derived growth factor C and several extracellular matrix genes as downstream targets of miR-29a involved in regulating ocular angiogenesis. Our data suggest that miR-29a may be a promising clinical candidate for the treatment of neovascular diseases.<\/jats:p>","DOI":"10.1073\/pnas.2204795119","type":"journal-article","created":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T14:50:06Z","timestamp":1667400606000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Anti-angiogenic properties of microRNA-29a in preclinical ocular models"],"prefix":"10.1073","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9333-4362","authenticated-orcid":false,"given":"De-Wei","family":"Peng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital of Wenzhou Medical University, Wenzhou, 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Lin","family":"Lan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital of Wenzhou Medical University, Wenzhou, 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling-Qin","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital of Wenzhou Medical University, Wenzhou, 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Xi","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital of Wenzhou Medical University, Wenzhou, 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital of Wenzhou Medical University, Wenzhou, 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5363-0557","authenticated-orcid":false,"given":"Robert J.","family":"D\u2019Amato","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Department of Surgery, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Department of Ophthalmology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3617-6425","authenticated-orcid":false,"given":"Zai-Long","family":"Chi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital of Wenzhou Medical University, Wenzhou, 325027, China"},{"name":"National Clinical Research Center for Ocular Diseases, Eye Hospital of Wenzhou Medical University, Wenzhou, 325027, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-013-0993-5"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2423(10)50006-4"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000320006"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.039"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2013.107"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2016.03.045"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1379"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2008.11.003"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-015-1940-0"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00478"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01655"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21020649"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00276"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2017.03.032"},{"key":"e_1_3_4_15_2","first-page":"866","article-title":"Evaluation of miR-29c inhibits endotheliocyte migration and angiogenesis of human endothelial cells by suppressing the insulin like growth factor 1","volume":"7","author":"Hu Y.","year":"2015","unstructured":"Y. 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