A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy
DC Field | Value | Language |
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dc.contributor.author | Sulaiman, Rania S. | - |
dc.contributor.author | Merrigan, Stephanie | - |
dc.contributor.author | Quigley, Judith | - |
dc.contributor.author | Qi, Xiaoping | - |
dc.contributor.author | Lee, Bit | - |
dc.contributor.author | Boulton, Michael E. | - |
dc.contributor.author | Kennedy, Breandan | - |
dc.contributor.author | Seo, Seung-Yong | - |
dc.contributor.author | Corson, Timothy W. | - |
dc.date.available | 2020-02-28T01:45:29Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2016-05-05 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/8274 | - |
dc.description.abstract | Ocular neovascularisation underlies blinding eye diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and wet age-related macular degeneration. These diseases cause irreversible vision loss, and provide a significant health and economic burden. Biologics targeting vascular endothelial growth factor (VEGF) are the major approach for treatment. However, up to 30% of patients are non-responsive to these drugs and they are associated with ocular and systemic side effects. Therefore, there is a need for small molecule ocular angiogenesis inhibitors to complement existing therapies. We examined the safety and therapeutic potential of SH-11037, a synthetic derivative of the antiangiogenic homoisoflavonoid cremastranone, in models of ocular neovascularisation. SH-11037 dose-dependently suppressed angiogenesis in the choroidal sprouting assay ex vivo and inhibited ocular developmental angiogenesis in zebrafish larvae. Additionally, intravitreal SH-11037 (1 mu M) significantly reduced choroidal neovascularisation (CNV) lesion volume in the laser-induced CNV mouse model, comparable to an anti-VEGF antibody. Moreover, SH11037 synergised with anti-VEGF treatments in vitro and in vivo. Up to 100 mu M SH-11037 was not associated with signs of ocular toxicity and did not interfere with retinal function or pre-existing retinal vasculature. SH-11037 is thus a safe and effective treatment for murine ocular neovascularisation, worthy of further mechanistic and pharmacokinetic evaluation. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.relation.isPartOf | SCIENTIFIC REPORTS | - |
dc.subject | MACULAR DEGENERATION | - |
dc.subject | CHOROIDAL NEOVASCULARIZATION | - |
dc.subject | RETINAL NEOVASCULARIZATION | - |
dc.subject | INTRAVITREAL INJECTION | - |
dc.subject | DIABETIC-RETINOPATHY | - |
dc.subject | ANGIOGENESIS | - |
dc.subject | HOMOISOFLAVANONE | - |
dc.subject | INHIBITION | - |
dc.subject | MECHANISMS | - |
dc.subject | MODEL | - |
dc.title | A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000375546300001 | - |
dc.identifier.doi | 10.1038/srep25509 | - |
dc.identifier.bibliographicCitation | SCIENTIFIC REPORTS, v.6 | - |
dc.identifier.scopusid | 2-s2.0-84966711484 | - |
dc.citation.title | SCIENTIFIC REPORTS | - |
dc.citation.volume | 6 | - |
dc.contributor.affiliatedAuthor | Seo, Seung-Yong | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | MACULAR DEGENERATION | - |
dc.subject.keywordPlus | CHOROIDAL NEOVASCULARIZATION | - |
dc.subject.keywordPlus | RETINAL NEOVASCULARIZATION | - |
dc.subject.keywordPlus | INTRAVITREAL INJECTION | - |
dc.subject.keywordPlus | DIABETIC-RETINOPATHY | - |
dc.subject.keywordPlus | ANGIOGENESIS | - |
dc.subject.keywordPlus | HOMOISOFLAVANONE | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | MECHANISMS | - |
dc.subject.keywordPlus | MODEL | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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