A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy
|Title:||A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy||Authors:||Sulaiman, Rania S.
|Permanent link:||http://hdl.handle.net/10197/8346||Date:||5-May-2016||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.||Type of material:||Journal Article||Publisher:||Nature Publishing Group||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|
|Appears in Collections:||Conway Institute Research Collection|
Biomolecular and Biomedical Science Research Collection
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