A peptide encoded by exon 6 of VEGF (EG3306) inhibits VEGF-induced angiogenesis in vitro and ischaemic retinal neovascularisation in vivo.
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.
Bainbridge
James W B
JW
Institute of Ophthalmology, Bath Street, London, UK.
Jia
Haiyan
H
Bagherzadeh
Azadeh
A
Selwood
David
D
Ali
Robin R
RR
Zachary
Ian
I
D000818:Animals; D002460:Cell Line; D016895:Culture Media, Serum-Free; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005091:Exons; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012160:Retina / Q000166:cytology / Q000473:pathology; D015861:Retinal Neovascularization / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016895:Culture Media, Serum-Free; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors