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Current Eye Research Volume 46, 2021 - Issue 10
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Novel Peptide NT/K-CFY Derived from Kringle Structure of Neurotrypsin Inhibits Neovascularization

Xieyi Yaoa Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;b National Clinical Research Center for Eye Diseases, Shanghai, China;c Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China;d Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China;e Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, ChinaORCID Iconhttps://orcid.org/0000-0002-0851-6840View further author information
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Chong Chena Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;b National Clinical Research Center for Eye Diseases, Shanghai, China;c Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China;d Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China;e Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, ChinaView further author information
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Jian Zhanga Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;b National Clinical Research Center for Eye Diseases, Shanghai, China;c Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China;d Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China;e Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, ChinaView further author information
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Yupeng Xua Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;b National Clinical Research Center for Eye Diseases, Shanghai, China;c Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China;d Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China;e Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, ChinaView further author information
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Shuyu Xionga Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;b National Clinical Research Center for Eye Diseases, Shanghai, China;c Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China;d Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China;e Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, ChinaView further author information
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Qing Gua Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;b National Clinical Research Center for Eye Diseases, Shanghai, China;c Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China;d Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China;e Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, ChinaView further author information
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Xun Xua Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;b National Clinical Research Center for Eye Diseases, Shanghai, China;c Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China;d Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China;e Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, ChinaCorrespondence[email protected]
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Yan Suoa Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;b National Clinical Research Center for Eye Diseases, Shanghai, China;c Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China;f Shanghai Eye Diseases Prevention and Treatment Center/Shanghai Eye Hospital, Shanghai, ChinaCorrespondence[email protected]
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Pages 1551-1558 | Received 01 Dec 2020, Accepted 11 Mar 2021, Published online: 19 Apr 2021
 
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ABSTRACT

Purpose: To assess the anti-neovascularization effect of a novel peptide NT/K-CFY derived from the kringle domain of neurotrypsin.

Materials and Methods: Cell migration, lumen formation and cell proliferation assays were performed to determine the anti-neovascularization effect of NT/K-CFY in primary human umbilical vein endothelial cells (HUVECs). Chick chorioallantoic membrane (CAM) and oxygen-induced retinopathy (OIR) models were established to assess the anti-angiogenic role of NT/K-CFY in vivo. The retinal expression of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) was examined by western blot and real-time PCR in OIR model.

Results: The in vitro results showed that NT/K-CFY effectively and safely decreased VEGF-induced cell migration, cell proliferation and tube formation in HUVECs. In addition, NT/K-CFY showed certain efficacy in angiogenesis inhibition in chicken embryos and oxygen-treated mouse pups. Moreover, the CFY peptide also improved retinal blood perfusion and reversed the abnormal expression of VEGF and PEDF in OIR mouse model.

Conclusion: NT/K-CFY peptide strongly inhibits neovascularization in vitro and vivo. This novel peptide may become a promising therapeutic agent for ocular angiogenesis-related diseases.

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Acknowledgments

We thank all the members of Shanghai Key Laboratory of Ocular Fundus Diseases for their technical assistance throughout the research.

Disclosure statement

No competing financial interests or personal relationships that could have appeared to influence the work exist in this paper.

Additional information

Funding

The project was sponsored by the Program (No. 81800835) of the National Natural Science Foundation of China. The funding source had no role in the study design, collection, analysis, interpretation of data, decision to publish, or preparation of the article.

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