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

Rania S. Sulaiman, Stephanie Merrigan, Judith Quigley, Xiaoping Qi, Bit Lee, Michael E. Boulton, Breandán Kennedy, Seung Yong Seo, Timothy Corson

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Article number25509
JournalScientific Reports
Volume6
DOIs
StatePublished - May 5 2016

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Vascular Endothelial Growth Factor A
Choroidal Neovascularization
Therapeutics
Retinopathy of Prematurity
Angiogenesis Inhibitors
Eye Diseases
Macular Degeneration
Zebrafish
Diabetic Retinopathy
Biological Products
Larva
Lasers
Pharmacokinetics
Economics
Safety
Antibodies
Health
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy. / Sulaiman, Rania S.; Merrigan, Stephanie; Quigley, Judith; Qi, Xiaoping; Lee, Bit; Boulton, Michael E.; Kennedy, Breandán; Seo, Seung Yong; Corson, Timothy.

In: Scientific Reports, Vol. 6, 25509, 05.05.2016.

Research output: Contribution to journalArticle

Sulaiman, RS, Merrigan, S, Quigley, J, Qi, X, Lee, B, Boulton, ME, Kennedy, B, Seo, SY & Corson, T 2016, 'A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy', Scientific Reports, vol. 6, 25509. https://doi.org/10.1038/srep25509
Sulaiman, Rania S. ; Merrigan, Stephanie ; Quigley, Judith ; Qi, Xiaoping ; Lee, Bit ; Boulton, Michael E. ; Kennedy, Breandán ; Seo, Seung Yong ; Corson, Timothy. / A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy. In: Scientific Reports. 2016 ; Vol. 6.
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