A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy
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Title: | A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy | Authors: | Sulaiman, Rania S.; Merrigan, Stephanie; Quigley, Judith; Kennedy, Breandán; et al. | Permanent link: | http://hdl.handle.net/10197/8346 | Date: | 5-May-2016 | Online since: | 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. | Funding Details: | 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 | Keywords: | Pharmacodynamics; Angiogenesis; Experimental models of disease; Macular degeneration; Retinal diseases | DOI: | 10.1038/srep25509 | Language: | en | Status of Item: | Peer reviewed | This item is made available under a Creative Commons License: | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ |
Appears in Collections: | Conway Institute Research Collection Biomolecular and Biomedical Science Research Collection |
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