Effects of inflammation in cultured retinal pigment epithelial cells by transcriptomics and mass spectrometry: Does Zn play a protective role? Marta Aranaz 1 , Ana Álvarez-Barrios 1,4 , Marta Costas-Rodríguez 2 , Lara Lobo 1 , Lydia Álvarez 4 , Héctor González-Iglesias 3,4,5 , Rosario Pereiro 1,4 , Frank Vanhaecke 2 1 Department of Physical and Analytical Chemistry, University of Oviedo, Spain. 2 Department of Chemistry, Atomic & Mass Spectrometry, Ghent University, Belgium. 3 Instituto Oftalmológico Fernández-Vega, Oviedo, Spain. 4 Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Spain. 5 Department of Technology and Biotechnology of Dairy Products, IPLA-CSIC, Villaviciosa, Spain During ageing, the retina is exposed to inflammation processes, resulting in cell damage and the onset of ocular disorders, such as Age-related macular degeneration (AMD) [1,2] .These processes may be accompanied by elemental and/or isotopic alterations of metals involved in retinal functions, such as Zn, which plays a pivotal role in phototransduction and neurotrasmission processes [3] . In this context, the study of isotope fractionation in in vitro cell culture models mimicking the human in vivo cultures has shown to provide valuable information for unraveling biochemical processes. Furthermore, Zn homeostatic fluctuations are mediated by metallothioneins and Zn transporters, also affected during ageing and disease. These alterations suggest that both transcriptome analysis and the study of Zn isotopic composition would help to understand the processes involved in the development of neurodegenerative diseases. In this context, we aim at investigating the effects of exogenously supplemented Zn and/or pro-inflammatory Interleukin-1α in an in vitro human retinal pigment epithelial cell culture. The effects of such exposure were tackled by transcriptomics and isotopic analysis. The results showed that these processes responded to inflammation at both RNA and Zn isotopic levels, by inducing immune and cytokine responses and leading to a lighter Zn isotopic composition respectively. Interestingly, this inflammation was partially attenuated by short-term This work was financially supported through project AYUD/2021/51289 (PCTI Program of the Government of the Principality of Asturias and FEDER Program of the European Union) and PID2019-107838RB-I00/Agencia Estatal de Investigación (AEI)/10.13039/501100011033) in Spain. M.A. acknowledges the University of Oviedo for the Ph.D. grant ref. PAPI-21-PF-05.Technical support provided by Servicios Científico-Técnicos of the University of Oviedo is acknowledged. References 1. E. Buschini, A. Piras, R. Nuzzi, A. Vercelli, Age related macular degeneration and drusen: neuroinflammation in the retina, Prog. Neurobiol. 95(1) (2011) 14-25. 2. A. Kauppinen, J.J Paterno, J. Blasiak, A. Salminen, K. Kaarniranta. Inflammation and its role in age-related macular degeneration, Cell. Mol. Life Sci. 73(9) (2016) 1765-86. 3. B.L. Vallee, K.H. Falchuck, The biochemical basis of zinc physiology, Physiol. Rev. 73 (1993) 79-118. 4. *Preference for a virtual presentation Zn supplementation. Acknowledgements
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