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Inhibition of Pathological Corneal Neovascularization by a Small Peptide Derived From Human Apolipoprotein (a) Kringle V

Wang, Zhongxiao MD*; Zhao, Hui MD, PhD*; Ma, Jian-xing MD, PhD; Xu, Xun MD*

doi: 10.1097/ICO.0000000000000032
Basic Investigation

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.

*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.

Reprints: Xun Xu, Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, China 200080 (e-mail: drxuxun@sjtu.edu.cn).

Supported by the National Natural Science Foundation of China (81170862 and 30930097) and Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.

The authors have no conflicts of interest to disclose.

Received June 12, 2013

Accepted October 09, 2013

© 2014 by Lippincott Williams & Wilkins.