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

Nutrients

EYE-RISK Consortium¹  AnnekeI. Den Hollander²  Franziska Klose³  Sascha Dammeier³  Marius Ueffing³  Elod Kortvely⁴  Eszter Emri⁵  David Simpson⁵  Imre Lengyel⁵ 

[1] ;Departments of Ophthalmology and Genetics, Radboud University Medical Center, 6525EX Nijmegen, The Netherlands;Institute for Ophthalmic Research, University of Tubingen, D-72076 Tubingen, Germany;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;Wellcome Wolfson Institute for Experimental Medicine, Queen’s University of Belfast, Belfast BT97BL, Northern Ireland, UK;

关键词: zinc;    retinal pigment epithelium;    age-related macular degeneration;    transcriptome;    proteome;    secretome;   

DOI  :  10.3390/nu12103051

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown