Sulaiman, Rania S.Merrigan, StephanieQuigley, JudithQi, XiaopingLee, BitBoulton, Michael E.Kennedy, BreandánSeo, Seung-YongCorson, Timothy W.2016-05-262016-05-262016-05-05Sulaiman, R. S., Merrigan, S., Quigley, J., Qi, X., Lee, B., Boulton, M. E., ... & Corson, T. W. (2016). A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy. Scientific Reports, 6, 25509. http://dx.doi.org/10.1038/srep25509.https://hdl.handle.net/1805/9681Ocular 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.enAttribution 3.0 United Statesneovascular eye diseaseanti-VEGF treatmentsArticle