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A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy
Date Issued
2016-05-05
Date Available
2017-02-15T12:49:12Z
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 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.
Other Sponsorship
International Retinal Research Foundation
Retina Research Foundation
Bright Focus Foundation
Ministry of Education
Research to Prevent Blindness, Inc.
NIH/NEI
Type of Material
Journal Article
Publisher
Nature Publishing Group
Journal
Scientific Reports
Volume
6
Issue
25509
Copyright (Published Version)
2016 the Authors
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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Owning collection
Scopus© citations
54
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