Altered zinc homeostasis in a primary cell culture model of the retinal pigment epithelium

Autor: Ana Álvarez-Barrios, Lydia Álvarez, Enol Artime, Montserrat García, Imre Lengyel, Rosario Pereiro, Héctor González-Iglesias
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Nutrition, Vol 10 (2023)
Druh dokumentu: article
ISSN: 2296-861X
DOI: 10.3389/fnut.2023.1124987
Popis: The retinal pigment epithelium (RPE) is progressively degenerated during age-related macular degeneration (AMD), one of the leading causes of irreversible blindness, which clinical hallmark is the buildup of sub-RPE extracellular material. Clinical observations indicate that Zn dyshomeostasis can initiate detrimental intracellular events in the RPE. In this study, we used a primary human fetal RPE cell culture model producing sub-RPE deposits accumulation that recapitulates features of early AMD to study Zn homeostasis and metalloproteins changes. RPE cell derived samples were collected at 10, 21 and 59 days in culture and processed for RNA sequencing, elemental mass spectrometry and the abundance and cellular localization of specific proteins. RPE cells developed processes normal to RPE, including intercellular unions formation and expression of RPE proteins. Punctate deposition of apolipoprotein E, marker of sub-RPE material accumulation, was observed from 3 weeks with profusion after 2 months in culture. Zn cytoplasmic concentrations significantly decreased 0.2 times at 59 days, from 0.264 ± 0.119 ng·μg−1 at 10 days to 0.062 ± 0.043 ng·μg−1 at 59 days (p
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