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Identification of age-associated proteins and functional alterations in human primary retinal pigment epithelium cells

View ORCID ProfileXiuxiu Jin, View ORCID ProfileJingyang Liu, View ORCID ProfileWeiping Wang, View ORCID ProfileJiangfeng Li, View ORCID ProfileGuangming Liu, View ORCID ProfileRuiqi Qiu, View ORCID ProfileMingzhu Yang, View ORCID ProfileMeng Liu, View ORCID ProfileLin Yang, View ORCID ProfileXiaofeng Du, View ORCID ProfileBo Lei
doi: https://doi.org/10.1101/2021.10.17.464744
Xiuxiu Jin
1Henan Provincial People’s Hospital, Henan Eye Hospital, Henan Eye Institute, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
2Henan Provincial People’s Hospital, Branch of National Clinical Research Center for Ocular Disease, Zhengzhou, Henan, 450003, China
3Henan Provincial People’s Hospital, Henan Eye Institute, School of Medicine, Henan University, Zhengzhou, Henan, 450003, China
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Jingyang Liu
1Henan Provincial People’s Hospital, Henan Eye Hospital, Henan Eye Institute, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
2Henan Provincial People’s Hospital, Branch of National Clinical Research Center for Ocular Disease, Zhengzhou, Henan, 450003, China
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Weiping Wang
1Henan Provincial People’s Hospital, Henan Eye Hospital, Henan Eye Institute, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
2Henan Provincial People’s Hospital, Branch of National Clinical Research Center for Ocular Disease, Zhengzhou, Henan, 450003, China
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Jiangfeng Li
5School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China
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Guangming Liu
1Henan Provincial People’s Hospital, Henan Eye Hospital, Henan Eye Institute, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
2Henan Provincial People’s Hospital, Branch of National Clinical Research Center for Ocular Disease, Zhengzhou, Henan, 450003, China
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Ruiqi Qiu
1Henan Provincial People’s Hospital, Henan Eye Hospital, Henan Eye Institute, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
2Henan Provincial People’s Hospital, Branch of National Clinical Research Center for Ocular Disease, Zhengzhou, Henan, 450003, China
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Mingzhu Yang
1Henan Provincial People’s Hospital, Henan Eye Hospital, Henan Eye Institute, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
2Henan Provincial People’s Hospital, Branch of National Clinical Research Center for Ocular Disease, Zhengzhou, Henan, 450003, China
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Meng Liu
1Henan Provincial People’s Hospital, Henan Eye Hospital, Henan Eye Institute, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
4Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China
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Lin Yang
1Henan Provincial People’s Hospital, Henan Eye Hospital, Henan Eye Institute, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
4Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China
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Xiaofeng Du
1Henan Provincial People’s Hospital, Henan Eye Hospital, Henan Eye Institute, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
2Henan Provincial People’s Hospital, Branch of National Clinical Research Center for Ocular Disease, Zhengzhou, Henan, 450003, China
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Bo Lei
1Henan Provincial People’s Hospital, Henan Eye Hospital, Henan Eye Institute, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
2Henan Provincial People’s Hospital, Branch of National Clinical Research Center for Ocular Disease, Zhengzhou, Henan, 450003, China
4Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, 450001, China
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  • For correspondence: bolei99@126.com
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Abstract

Background Retinal pigmented epithelium (RPE) has essential functions to nourish and support the neural retina, and is of vital importance in the pathogenesis of age-related retinal degeneration. However, the exact molecular changes of RPE in aging remain poorly defined.

Methods We isolated human primary RPE (hRPE) cells from 18 eye donors distributed over a wide age range (10 - 67 years). A quantitative proteomic analysis was performed to analyze their intracellular and secreted protein changes, and potential age-associtated mechanisms were validated by ARPE-19 and hRPE cells.

Results Age-stage related subtypes and age-associtated proteins and functional alterations were revealed. Proteomic data and verifications showed that RNF123 and RNF149 related ubiquitin-mediated proteolysis might be an important clearance mechanism in elimination of oxidative damaged proteins in aged hRPE. In older hRPE cells, apoptotic signaling related pathways were up-regulated and endoplasmic reticulum organization was down-regulated both in intracellular and secreted proteome.

Conclusions This work paints a detailed molecular picture of human RPE in aging process and provides new insights for molecular characteristics of RPE in aging and related clinical retinal conditions.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 18, 2021.
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Identification of age-associated proteins and functional alterations in human primary retinal pigment epithelium cells
Xiuxiu Jin, Jingyang Liu, Weiping Wang, Jiangfeng Li, Guangming Liu, Ruiqi Qiu, Mingzhu Yang, Meng Liu, Lin Yang, Xiaofeng Du, Bo Lei
bioRxiv 2021.10.17.464744; doi: https://doi.org/10.1101/2021.10.17.464744
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Identification of age-associated proteins and functional alterations in human primary retinal pigment epithelium cells
Xiuxiu Jin, Jingyang Liu, Weiping Wang, Jiangfeng Li, Guangming Liu, Ruiqi Qiu, Mingzhu Yang, Meng Liu, Lin Yang, Xiaofeng Du, Bo Lei
bioRxiv 2021.10.17.464744; doi: https://doi.org/10.1101/2021.10.17.464744

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