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Michael R. R. Böhm, Karina Hadrian, Stefan Schlatt, Joachim Wistuba, Solon Thanos, Simone König; Age-related topographic protein profiling of the retinal pigment epithelium of macular-bearing Callithrix jacchus. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3982.
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© ARVO (1962-2015); The Authors (2016-present)
In the retinal pigment epithelium (RPE), extensive light exposure and increased metabolism in the macular compared to peripheral regions cause a different physiological aging process. The underlying molecular mechanisms during aging in the context of topography are not well known. The aim of this study was to determine age-related alterations of the proteome of the RPE of common macular-bearing marmosets (Callithrix jacchus) under topographic conditions.
The RPE was removed from eyecups of neonatal, adult, and senile C. jacchus (n=3 each). Macular and peripheral regions were separated and proteins were isolated from the tissue homogenates. Samples were prepared for ion mobility MS (IMS) tandem analysis (M-Class, Synapt G2 Si, Waters Corp.) by alkylation and tryptic cleavage. The results of the 2 h IMS-runs were subjected to peak picking, database searching (Uniprot human and C. jacchus) and statistical analyzed (Progenesis) followed by pathway analysis (Panther, Impala) and data visualization (Visumap). Only proteins contributing to clustering with fold changes ≥ 2 and ANOVA p ≤ 0.05 were further analyzed.
Protein profiles of macular and periphery of neonate RPE were different compared to aged tissues. As demonstrated by principal component analysis, the topology of the samples within adult/senile eyes has a higher impact on altered protein profiles than the different ages of the analysed eyes. Proteins, upregulated in neonate RPE compared to adult/senile tissue (e.g., HSP 90), could be associated with developmental processes. In senile probes, proteins related to oxidative stress (e.g., hexokinase-1), inflammatory response (e.g., annexin A1), and angiostasis (e.g., thrombospondin-1) were of more importance in the macular. Pathway analysis of aged macular proteins unveiled alterations, e.g., p53-signaling.
The study unveils alterations of proteomic footprint in the aging RPE related to different anatomical regions. A better understanding could yield predictive factors to detect the conversion of physiological aging into pathological conditions. A more targeted investigation of individual proteins is still needed to elucidate their role within the aging process and to possibly yield predictive factors for the conversion of physiological aging into pathological conditions. Supported by the German Research Foundation (DFG; BO-4661/-1).
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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