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Open AccessArticle

A Multi-Omics Approach Identifies Key Regulatory Pathways Induced by Long-Term Zinc Supplementation in Human Primary Retinal Pigment Epithelium

1
Wellcome Wolfson Institute for Experimental Medicine, Queen’s University of Belfast, Belfast BT97BL, Northern Ireland, UK
2
Roche Pharma Research and Early Development, Immunology, Infectious Diseases and Ophthalmology (I2O) Discovery and Translational Area, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland
3
Institute for Ophthalmic Research, University of Tubingen, D-72076 Tubingen, Germany
4
Departments of Ophthalmology and Genetics, Radboud University Medical Center, 6525EX Nijmegen, The Netherlands
*
Author to whom correspondence should be addressed.
Membership of the EYE-RISK Consortium is provided in the acknowledgments.
Nutrients 2020, 12(10), 3051; https://doi.org/10.3390/nu12103051
Received: 17 September 2020 / Revised: 1 October 2020 / Accepted: 1 October 2020 / Published: 6 October 2020
(This article belongs to the Special Issue Nutrition for Eye Health)
In age-related macular degeneration (AMD), both systemic and local zinc levels decline. Elevation of zinc in clinical studies delayed the progression to end-stage AMD. However, the molecular pathways underpinning this beneficial effect are not yet identified. In this study, we used differentiated primary human fetal retinal pigment epithelium (RPE) cultures and long-term zinc supplementation to carry out a combined transcriptome, proteome and secretome analysis from three genetically different human donors. After combining significant differences, we identified the complex molecular networks using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). The cell cultures from the three donors showed extensive pigmentation, development of microvilli and basal infoldings and responded to zinc supplementation with an increase in transepithelial electrical resistance (TEER) (apical supplementation: 443.2 ± 79.3%, basal supplementation: 424.9 ± 116.8%, compared to control: 317.5 ± 98.2%). Significant changes were observed in the expression of 1044 genes, 151 cellular proteins and 124 secreted proteins. Gene set enrichment analysis revealed changes in specific molecular pathways related to cell adhesion/polarity, extracellular matrix organization, protein processing/transport, and oxidative stress response by zinc and identified a key upstream regulator effect similar to that of TGFB1. View Full-Text
Keywords: zinc; retinal pigment epithelium; age-related macular degeneration; transcriptome; proteome; secretome; gene set enrichment; TGFB1 zinc; retinal pigment epithelium; age-related macular degeneration; transcriptome; proteome; secretome; gene set enrichment; TGFB1
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MDPI and ACS Style

Emri, E.; Kortvely, E.; Dammeier, S.; Klose, F.; Simpson, D.; Consortium, E.-R.; den Hollander, A.I.; Ueffing, M.; Lengyel, I. A Multi-Omics Approach Identifies Key Regulatory Pathways Induced by Long-Term Zinc Supplementation in Human Primary Retinal Pigment Epithelium. Nutrients 2020, 12, 3051.

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