PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis
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Full-length article|更新时间:2023-08-29
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PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis
Genes & DiseasesVol. 10, Issue 4, (2023)
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
Jingyi Luo, Qing Lian, Deliang Zhu, et al. PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis. [J]. Genes & Diseases 10(4).(2023)
DOI:
Jingyi Luo, Qing Lian, Deliang Zhu, et al. PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis. [J]. Genes & Diseases 10(4).(2023) DOI: 10.1016/j.gendis.2022.05.036.
PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis
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.
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