Suppression of choroidal neovascularization and epithelial-mesenchymal transition in retinal pigmented epithelium by adeno-associated virus-mediated overexpression of CCN5 in mice
DC Field | Value | Language |
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dc.contributor.author | Im, Sora | - |
dc.contributor.author | Han, Jung Woo | - |
dc.contributor.author | Park, Euy Jun | - |
dc.contributor.author | Bang, Ji Hong | - |
dc.contributor.author | Shin, Hee Jeong | - |
dc.contributor.author | Chang, Hun Soo | - |
dc.contributor.author | Woo, Kee Min | - |
dc.contributor.author | Park, Woo Jin | - |
dc.contributor.author | Park, Tae Kwann | - |
dc.date.accessioned | 2022-09-06T06:42:13Z | - |
dc.date.available | 2022-09-06T06:42:13Z | - |
dc.date.issued | 2022-06 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/21391 | - |
dc.description.abstract | Choroidal neovascularization (CNV) is a defining characteristic feature of neovascular age-related macular degeneration (nAMD) that frequently results in irreversible vision loss. The current strategies for the treatment of nAMD are mainly based on neutralizing vascular endothelial growth factor (VEGF). However, anti-VEGF therapies are often associated with subretinal fibrosis that eventually leads to damages in macula. In this study, we tested whether an anti-fibrotic and anti-angiogenic protein CCN5 can potentially be an effective and safe therapeutic modality in a mouse model of CNV. Laser photocoagulation was utilized to induce CNV, which was followed by intravitreal injection of recombinant adeno-associated virus serotype 2 encoding CCN5 (rAAV2-CCN5). Our data demonstrated that rAAV2-CCN5, but not a control viral vector, rAAV2-VLP, prominently attenuated both CNV lesions and angiogenesis. Aflibercept, which was utilized as a positive control, exhibited similar effects on CNV lesions and angiogenesis in our experimental settings. Upon laser photocoagulation, retinal pigmented epithelium (RPE) cells underwent significant morphological changes including cellular enlargement and loss of hexagonality. rAAV2-CCN5 significantly normalized these morphological defects. Laser photocoagulation also led to fibrotic deformation in RPE cells through inducing epithelial-mesenchymal transition (EMT), which was completely blocked by rAAV2-CCN5. In a striking contrast, aflibercept as well as rAAV2-VLP failed to exhibit any effects on EMT. Collectively, this study suggest that CCN5 might provide a potential novel strategy for the treatment of nAMD with a capability to inhibit CNV and fibrosis simaultaneously. | - |
dc.format.extent | 16 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Public Library of Science | - |
dc.title | Suppression of choroidal neovascularization and epithelial-mesenchymal transition in retinal pigmented epithelium by adeno-associated virus-mediated overexpression of CCN5 in mice | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1371/journal.pone.0269937 | - |
dc.identifier.scopusid | 2-s2.0-85132046397 | - |
dc.identifier.wosid | 000843575700154 | - |
dc.identifier.bibliographicCitation | PLoS ONE, v.17, no.6, pp 1 - 16 | - |
dc.citation.title | PLoS ONE | - |
dc.citation.volume | 17 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 16 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | ENDOTHELIAL GROWTH-FACTOR | - |
dc.subject.keywordPlus | MACULAR DEGENERATION | - |
dc.subject.keywordPlus | GENE-THERAPY | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | TRANSDUCTION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | MANAGEMENT | - |
dc.subject.keywordPlus | RESPONSES | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.subject.keywordPlus | FIBROSIS | - |
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