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

xiuxiu, j.; Jingyang, L.; Weiping, W.; Jiangfeng, L.; Guangming, L.; Ruiqi, Q.; Mingzhu, Y.; Meng, L.; Lin, Y.; Xiaofeng, D.; Bo, L.

doi:10.1101/2021.10.17.464744

bioRxiv · 10.1101/2021.10.17.464744

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

xiuxiu, j.·Jingyang, L.·Weiping, W.·Jiangfeng, L.·Guangming, L.·Ruiqi, Q.·Mingzhu, Y.·Meng, L.·Lin, Y.·Xiaofeng, D.·Bo, L.

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Abstract

BackgroundRetinal 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. MethodsWe 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. ResultsAge-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. ConclusionsThis 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.

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xiuxiu, j., Jingyang, L., Weiping, W., Jiangfeng, L., Guangming, L., Ruiqi, Q., Mingzhu, Y., Meng, L., Lin, Y., Xiaofeng, D., Bo, L.. 2021-10-18. Identification of age-associated proteins and functional alterations in human primary retinal pigment epithelium cells. https://doi.org/10.1101/2021.10.17.464744

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