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Science China. Life sciences
06, 2022;65 (6): 1157-1170.

CD146 as a promising therapeutic target for retinal and choroidal neovascularization diseases.

Bai Xue, Ping Wang, Wenzhen Yu, Jing Feng, Jie Li, Rulian Zhao, Zhenglin Yang, Xiyun Yan, Hongxia Duan
Author Information
  1. Bai Xue: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China.
  2. Ping Wang: Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  3. Wenzhen Yu: Department of Ophthalmology, People's Hospital, Peking University, Beijing, 100044, China.
  4. Jing Feng: Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
  5. Jie Li: Department of Ophthalmology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.
  6. Rulian Zhao: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China.
  7. Zhenglin Yang: Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, China. zliny@yahoo.com.
  8. Xiyun Yan: Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. yanxy@ibp.ac.cn.
  9. Hongxia Duan: Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. cherryshoen@aliyun.com.
PMID: 34729700 DOI: 10.1007/s11427-021-2020-0

Abstract

Blood vessel dysfunction causes several retinal diseases, including diabetic retinopathy, familial exudative vitreoretinopathy, macular degeneration and choroidal neovascularization in pathological myopia. Vascular endothelial growth factor (VEGF)-neutralizing proteins provide benefits in most of those diseases, yet unsolved haemorrhage and frequent intraocular injections still bothered patients. Here, we identified endothelial CD146 as a new target for retinal diseases. CD146 expression was activated in two ocular pathological angiogenesis models, a laser-induced choroid neovascularization model and an oxygen-induced retinopathy model. The absence of CD146 impaired hypoxia-induced cell migration and angiogenesis both in cell lines and animal model. Preventive or therapeutic treatment with anti-CD146 antibody AA98 significantly inhibited hypoxia-induced aberrant retinal angiogenesis in two retinal disease models. Mechanistically, under hypoxia condition, CD146 was involved in the activation of NFκB, Erk and Akt signalling pathways, which are partially independent of VEGF. Consistently, anti-CD146 therapy combined with anti-VEGF therapy showed enhanced impairment effect of hypoxia-induced angiogenesis in vitro and in vivo. Given the critical role of abnormal angiogenesis in retinal and choroidal diseases, our results provide novel insights into combinatorial therapy for neovascular fundus diseases.

Keywords

CD146 VEGF angiogenesis combined treatment ocular diseases

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MeSH Term

Animals
CD146 Antigen
Choroid Diseases
Choroidal Neovascularization
Humans
Hypoxia
Neovascularization, Pathologic
Retinal Diseases
Retinal Neovascularization
Vascular Endothelial Growth Factor A

Chemicals

CD146 Antigen
Vascular Endothelial Growth Factor A
Journal Article

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