A peptide encoded by exon 6 of VEGF (EG3306) inhibits VEGF-induced angiogenesis in vitro and ischaemic retinal neovascularisation in vivo |
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Authors: | Bainbridge James W B Jia Haiyan Bagherzadeh Azadeh Selwood David Ali Robin R Zachary Ian |
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Institution: | Institute of Ophthalmology, Bath Street, London, UK. |
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Abstract: | VEGF is an important mediator of pathological angiogenesis in the eye and is a target for the development of novel anti-angiogenic molecules. In a previous study we identified 12-amino acid peptides derived from exon 6 of VEGF that inhibited VEGF binding to its receptors in HUVECs, endothelial cell functions, and in vitro angiogenesis. Screening of a series of truncated peptides corresponding to the inhibitory region of exon 6 identified a seven amino acid residue peptide, RKRKKSR, as the minimum exon 6-encoded sequence which retains the ability to inhibit VEGF receptor binding and angiogenesis in vitro. The effect of the seven-residue peptide was examined in a mouse model of ischaemic retinal neovascularisation. Administration of the peptide caused a 50% inhibition of retinal neovascularisation and was as effective in inhibiting ischaemic angiogenesis as soluble Flt-1 adenovirus. These results demonstrate that a seven amino acid VEGF exon 6-derived peptide is an effective inhibitor of ocular neovascularisation in vivo, and may have applications in the treatment of pathophysiological ocular neovascularisation in human disease. |
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Keywords: | Endothelium KDR EG3306 |
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