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

Files in This Item:
 File SizeFormat
DownloadSulaiman_2016_srep25509.pdf2.14 MBAdobe PDF
Title: A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy
Authors: Sulaiman, Rania S.Merrigan, StephanieQuigley, JudithKennedy, Breandánet 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: PharmacodynamicsAngiogenesisExperimental models of diseaseMacular degenerationRetinal 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

Show full item record

SCOPUSTM   
Citations 10

31
Last Week
0
Last month
checked on Sep 11, 2020

Page view(s)

1,438
Last Week
3
Last month
20
checked on Jun 26, 2022

Download(s)

230
checked on Jun 26, 2022

Google ScholarTM

Check

Altmetric


If you are a publisher or author and have copyright concerns for any item, please email research.repository@ucd.ie and the item will be withdrawn immediately. The author or person responsible for depositing the article will be contacted within one business day.