Journal
CORNEA
Volume 33, Issue 4, Pages 405-413Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/ICO.0000000000000032
Keywords
angiogenesis; peptide; corneal neovascularization
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Funding
- National Natural Science Foundation of China [81170862, 30930097]
- Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
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PURPOSE: 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
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