PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis

Jingyi Luo; Qing Lian; Deliang Zhu; Minglei Zhao; Tingfang Mei; Bizhi Shang; Zeqiu Yang; Chujun Liu; Wenchang Xu; Lan Zhou; Keling Wu; Xinqi Liu; Yuhua Lai; Fuxiang Mao; Weihua Li; Chengguo Zuo; Kang Zhang; Mingkai Lin; Yehong Zhuo; Yizhi Liu; Ling Zhao

doi:10.1016/j.gendis.2022.05.036

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PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis

Full-length article | 更新时间：2023-08-29

- PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis
- PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis
- Genes & Diseases 2023年10卷第4期
- 作者机构：
  
  1. Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University,Guangdong,Guangzhou,China,510000
  2. Guangzhou Regenerative Medicine and Health Guangdong Laboratory,Guangdong,Guangzhou,China,510530
  3. Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences,Guangdong,Guangzhou,China,510080
  4. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science,Guangdong,Guangzhou,China,510060
  5. Department of Ophthalmology, Huizhou Municipal Central Hospital,Guangdong,Huizhou,China,516000
  6. Center for Biomedicine and Innovations, Faculty of Medicine, Macau University of Science and Technology, Macau,China,999078
  7. Dongguan Guangming Ophthalmic Hospital,Dongguan,China,523000
  8. Research Unit of Ocular Development and Regeneration, Chinese Academy of Medical Sciences,Guangdong,Guangzhou,China,510060
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2022.05.036
  中图分类号：
- 纸质出版日期：2023，
  
  网络出版日期：2023-7-1，
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Jingyi Luo, Qing Lian, Deliang Zhu, 等. PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis[J]. Genes & Diseases, 2023,10(4).

Jingyi Luo, Qing Lian, Deliang Zhu, et al. PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis[J]. Genes & Diseases, 2023,10(4).
Jingyi Luo, Qing Lian, Deliang Zhu, 等. PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis[J]. Genes & Diseases, 2023,10(4). DOI： 10.1016/j.gendis.2022.05.036.

Jingyi Luo, Qing Lian, Deliang Zhu, et al. PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis[J]. Genes & Diseases, 2023,10(4). DOI： 10.1016/j.gendis.2022.05.036.

摘要

Abstract

Glaucoma is the leading cause of irreversible blindness worldwide. In the pathogenesis of glaucoma

activated microglia can lead to retinal ganglion cells (RGCs) apoptosis and death

however

the molecular mechanisms remain largely unknown. We demonstrate that phospholipid scramblase 1 (PLSCR1) is a key regulator promoting RGCs apoptosis and their clearance by microglia. As evidenced in retinal progenitor cells and RGCs of the acute ocular hypertension (AOH) mouse model

overexpressed PLSCR1 induced its translocation from the nucleus to the cytoplasm and cytomembrane

as well as elevated phosphatidylserine exposure and reactive oxygen species generation with subsequent RGCs apoptosis and death. These damages were effectively attenuated by PLSCR1 inhibition. In the AOH model

PLSCR1 led to an increase in M1 type microglia activation and retinal neuroinflammation. Upregulation of PLSCR1 resulted in strongly elevated phagocytosis of apoptotic RGCs by activated microglia. Taken together

our study provides important insights linking activated microglia to RGCs death in the glaucoma pathogenesis and other RGC-related neurodegenerative diseases.

关键词

Keywords

ApoptosisGlaucomaPhagocytosisPLSCR1Retinal ganglion cells

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