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Biochim Biophys Acta Mol Basis Dis ; 1866(10): 165843, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32454166

ABSTRACT

Age related macular degeneration (AMD) is a multifactorial disease with genetic, biochemical and environmental risk factors. We observed a significant increase in copper levels in choroid-RPE from donor eyeballs with AMD. Adult retinal pigment epithelial cells (ARPE19 cells) exposed to copper in-vitro showed a 2-fold increase in copper influx transporter CTR1 and copper uptake at 50 µM concentration. Further there was 2-fold increase in cytochrome C oxidase activity and a 2-fold increase in the mRNA expression of NRF 2 with copper treatment. There was a significant increase in mitochondrial biogenesis markers PGC1ß and TFAM which was confirmed by mitochondrial mass and copy number. On the contrary, in AMD choroid-RPE, the CTR1 mRNA was found to be significantly down-regulated compared to its respective controls. SCO1 and PGC1ß mRNA showed an increase in choroid-RPE. Our study proposes copper to play an important role in mitochondrial biogenesis in RPE cells.


Subject(s)
Copper/metabolism , Epithelial Cells/metabolism , Macular Degeneration/metabolism , Mitochondria/metabolism , Organelle Biogenesis , Retinal Pigment Epithelium/metabolism , Retinal Pigments/metabolism , Aged , Aged, 80 and over , Cell Line , Choroid/metabolism , Copper/pharmacology , Copper Transporter 1/metabolism , DNA-Binding Proteins/metabolism , Electron Transport Complex IV/metabolism , Female , Gene Expression Regulation/drug effects , Humans , Macular Degeneration/pathology , Male , Mitochondria/genetics , Mitochondrial Proteins/metabolism , Molecular Chaperones/metabolism , NF-E2-Related Factor 2/metabolism , RNA, Messenger/metabolism , RNA-Binding Proteins/metabolism , Reactive Oxygen Species/metabolism , Retinal Pigment Epithelium/pathology , Retinal Pigments/genetics , Transcription Factors/metabolism
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