Frontiers in Cell and Developmental Biology (Feb 2021)
SLC7A11 Reduces Laser-Induced Choroidal Neovascularization by Inhibiting RPE Ferroptosis and VEGF Production
- Xiaohuan Zhao,
- Xiaohuan Zhao,
- Xiaohuan Zhao,
- Xiaohuan Zhao,
- Min Gao,
- Min Gao,
- Min Gao,
- Min Gao,
- Jian Liang,
- Jian Liang,
- Jian Liang,
- Jian Liang,
- Yuhong Chen,
- Yuhong Chen,
- Yuhong Chen,
- Yuhong Chen,
- Yimin Wang,
- Yimin Wang,
- Yimin Wang,
- Yimin Wang,
- Yuwei Wang,
- Yuwei Wang,
- Yuwei Wang,
- Yuwei Wang,
- Yushu Xiao,
- Yushu Xiao,
- Yushu Xiao,
- Yushu Xiao,
- Zhenzhen Zhao,
- Zhenzhen Zhao,
- Zhenzhen Zhao,
- Zhenzhen Zhao,
- Xiaoling Wan,
- Xiaoling Wan,
- Xiaoling Wan,
- Xiaoling Wan,
- Mei Jiang,
- Mei Jiang,
- Mei Jiang,
- Mei Jiang,
- Xueting Luo,
- Xueting Luo,
- Xueting Luo,
- Xueting Luo,
- Feng Wang,
- Xiaodong Sun,
- Xiaodong Sun,
- Xiaodong Sun,
- Xiaodong Sun
Affiliations
- Xiaohuan Zhao
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Xiaohuan Zhao
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Xiaohuan Zhao
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Xiaohuan Zhao
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Min Gao
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Min Gao
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Min Gao
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Min Gao
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Jian Liang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Jian Liang
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Jian Liang
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Jian Liang
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Yuhong Chen
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Yuhong Chen
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Yuhong Chen
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Yuhong Chen
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Yimin Wang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Yimin Wang
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Yimin Wang
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Yimin Wang
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Yuwei Wang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Yuwei Wang
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Yuwei Wang
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Yuwei Wang
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Yushu Xiao
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Yushu Xiao
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Yushu Xiao
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Yushu Xiao
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Zhenzhen Zhao
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Zhenzhen Zhao
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Zhenzhen Zhao
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Zhenzhen Zhao
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Xiaoling Wan
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Xiaoling Wan
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Xiaoling Wan
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Xiaoling Wan
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Mei Jiang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Mei Jiang
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Mei Jiang
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Mei Jiang
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Xueting Luo
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Xueting Luo
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Xueting Luo
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Xueting Luo
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Feng Wang
- The Center for Microbiota and Immunological Diseases, Shanghai General Hospital, Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Xiaodong Sun
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Xiaodong Sun
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Xiaodong Sun
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Xiaodong Sun
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- DOI
- https://doi.org/10.3389/fcell.2021.639851
- Journal volume & issue
-
Vol. 9
Abstract
In age-related macular degeneration (AMD), one of the principal sources of vascular endothelial growth factor (VEGF) is retinal pigment epithelium (RPE) cells under hypoxia or oxidative stress. Solute carrier family 7 member 11 (SLC7A11), a key component of cystine/glutamate transporter, regulates the level of cellular lipid peroxidation, and restrains ferroptosis. In our study, we assessed the role of SLC7A11 in laser-induced choroidal neovascularization (CNV) and explored the underlying mechanism. We established a mouse model of CNV to detect the expression level of SLC7A11 and VEGF during disease progression. We found the expression of the SLC7A11 protein in RPE cells peaked at 3 days after laser treatment, which was correlated with the expression of VEGF. Intraperitoneal injection of SLC7A11 inhibitor expanded the area of CNV. We examined functional proteins related to oxidative stress and Fe2+ and found laser-induced ferroptosis accompanied by increased Fe2+ content and GPX4 expression in the RPE-choroidal complex after laser treatment. We verified the expression of SLC7A11 in the ARPE19 cell line and the effects of its inhibitors on cell viability and lipid peroxidation in vitro. Application of SLC7A11 inhibitor and SLC7A11 knockdown increased the level of lipid peroxidation and reduced the cell viability of ARPE19 which can be rescued by ferroptosis inhibitors ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1). Conversely, SLC7A11 overexpression induced resistance to erastin or RSL3-induced ferroptosis. Moreover, we tested the possible regulatory transcription factor NF-E2-related factor 2 (NRF2) of SLC7A11 by Western blot. Knock-down of NRF2 decreased the expression of SLC7A11. Our study suggests that SLC7A11 plays a key role in the laser-induced CNV model by protecting RPE cells from ferroptosis. SLC7A11 provides a new therapeutic target for neovascular AMD patients.
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