Inhibition of pathological corneal neovascularization by a small peptide derived from human apolipoprotein (a) Kringle V.
OBJECTIVE
The aim of this study was to evaluate the antiangiogenic activity of AU6, a novel 6-amino acid peptide derived from Kringle V of human apolipoprotein (a).


METHODS
RF/6A rhesus macaque choroid endothelial cells were used for in vitro studies. MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assays and modified Boyden chamber and Matrigel assays were used to evaluate the inhibitory effect of AU6 on vascular endothelial growth factor (VEGF)-stimulated endothelial cell functions, including cell proliferation, migration, and tube formation. The chick chorioallantoic membrane model, micropocket corneal neovascularization (CNV) model, and alkali burn CNV model were evaluated in vivo. Bevacizumab (Avastin), the VEGF-neutralizing antibody, and a scrambled peptide (AU6s) were used as positive and negative controls, respectively.


RESULTS
AU6 inhibited VEGF-induced RF/6A cell migration, proliferation, and tube formation. It also reduced pathological neovascularization in the chorioallantoic membrane model and in the 2 CNV models, that is, the mouse corneal micropocket model and the rat cornea alkali burn model.


CONCLUSIONS
AU6 effectively inhibited pathogenic CNV. This novel peptide shows potential as a new treatment for ocular neovascularization.
*Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China; and †Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
Zhongxiao
Z
Wang
Hui
H
Zhao
Jian-Xing
JX
Ma
Xun
X
Xu
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D053241:Apoprotein(a) / Q000737:chemistry / Q000494:pharmacology*; D000068258:Bevacizumab; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D002829:Choroid / Q000098:blood supply; D003094:Collagen; D016510:Corneal Neovascularization / Q000517:prevention & control*; D004195:Disease Models, Animal; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D018082:Kringles; D007797:Laminin; D008253:Macaca mulatta; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D011509:Proteoglycans; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; D007797:Laminin; D009842:Oligopeptides; D011509:Proteoglycans; D013778:Tetrazolium Salts; D013844:Thiazoles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; C070380:3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; D000068258:Bevacizumab; D003094:Collagen; D053241:Apoprotein(a)