期刊
JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
卷 37, 期 7, 页码 412-420出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/jop.2020.0120
关键词
peptide; neurotrypsin; kringle; NT; K-CRS; neovascularization
资金
- National Natural Science Foundation of China Program [81800835]
- Shanghai Sailing Program [18YF1419700]
- National Key R&D Program of China [2016YFC0904800, 2019YFC0840607]
- National Science and Technology Major Project of China [2017ZX09304010]
This study assessed the anti-neovascularization effect of a novel peptide NT/K-CRS in vitro and in vivo, showing that the peptide effectively inhibited new blood vessel formation with minor effects on cell proliferation and viability, indicating its potential therapeutic value for neovascular-related ocular diseases.
Purpose: To assess the anti-neovascularization effect of a novel peptide NT/K-CRS derived from the kringle domain of neurotrypsin in vitro and in vivo. Methods: Primary human umbilical vein endothelial cells (HUVECs) were treated with vascular endothelial growth factor (VEGF) in advance. Cell migration, lumen formation, and cell proliferation assays were performed to determine the anti-neovascularization effect of NT/K-CRS in HUVECs. TUNEL and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium tests were conducted to evaluate cell viability. Chick chorioallantoic membrane and oxygen-induced retinopathy model were established to assess the anti-angiogenic role of NT/K-CRS in vivo. Results: The in vitro results showed that NT/K-CRS effectively decreased VEGF-induced cell migration and endothelial tube formation, with no significant effect on cell proliferation and cell viability. In addition, NT/K-CRS showed great efficacy in angiogenesis inhibition in chicken embryos. The cytokine release syndrome (CRS) peptide also inhibited retinal neovascularization and improved retinal blood perfusion in oxygen-treated mouse pups through intravitreal injection. Conclusions: NT/K-CRS peptide derived from the kringle domain of neurotrypsin can strongly inhibit neovascularization in vitro and vivo. This novel peptide may become a promising therapeutic agent for neovascular-related ocular diseases.
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