RT Journal Article SR Electronic T1 Identification of age-associated proteins and functional alterations in human primary retinal pigment epithelium cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.10.17.464744 DO 10.1101/2021.10.17.464744 A1 Xiuxiu Jin A1 Jingyang Liu A1 Weiping Wang A1 Jiangfeng Li A1 Guangming Liu A1 Ruiqi Qiu A1 Mingzhu Yang A1 Meng Liu A1 Lin Yang A1 Xiaofeng Du A1 Bo Lei YR 2021 UL http://biorxiv.org/content/early/2021/10/18/2021.10.17.464744.abstract AB 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 StatementThe authors have declared no competing interest.