A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy

DC FieldValueLanguage
dc.contributor.authorSulaiman, Rania S.-
dc.contributor.authorMerrigan, Stephanie-
dc.contributor.authorQuigley, Judith-
dc.contributor.authorKennedy, Breandán-
dc.contributor.authoret al.-
dc.date.accessioned2017-02-15T12:49:12Z-
dc.date.available2017-02-15T12:49:12Z-
dc.date.copyright2016 the Authorsen
dc.date.issued2016-05-05-
dc.identifier.citationScientific Reportsen
dc.identifier.urihttp://hdl.handle.net/10197/8346-
dc.description.abstractOcular 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 μM) significantly reduced choroidal neovascularisation (CNV) lesion volume in the laser-induced CNV mouse model, comparable to an anti-VEGF antibody. Moreover, SH-11037 synergised with anti-VEGF treatments in vitro and in vivo. Up to 100 μM 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.en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.subjectPharmacodynamicsen
dc.subjectAngiogenesisen
dc.subjectExperimental models of diseaseen
dc.subjectMacular degenerationen
dc.subjectRetinal diseasesen
dc.titleA novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapyen
dc.typeJournal Articleen
dc.internal.authorcontactotherbrendan.kennedy@ucd.ie-
dc.statusPeer revieweden
dc.identifier.volume6en
dc.identifier.issue25509en
dc.identifier.doi10.1038/srep25509-
dc.neeo.contributorSulaiman|Rania S.|aut|-
dc.neeo.contributorMerrigan|Stephanie|aut|-
dc.neeo.contributorQuigley|Judith|aut|-
dc.neeo.contributorKennedy|Breandán|aut|-
dc.neeo.contributoret al.||aut|-
dc.description.othersponsorshipInternational Retinal Research Foundationen
dc.description.othersponsorshipRetina Research Foundationen
dc.description.othersponsorshipBright Focus Foundationen
dc.description.othersponsorshipMinistry of Educationen
dc.description.othersponsorshipResearch to Prevent Blindness, Inc.en
dc.description.othersponsorshipNIH/NEIen
dc.internal.rmsid618960184-
dc.date.updated2017-01-05T11:25:03Z-
dc.rights.licensehttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/en
item.grantfulltextopen-
item.fulltextWith Fulltext-
Appears in Collections:Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection
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