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 PGC1β 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 PGC1β mRNA showed an increase in choroid-RPE. Our study proposes copper to play an important role in mitochondrial biogenesis in RPE cells.
Keywords:
AMD; Copper; Mitochondrial biogenesis.
Copyright © 2020 Elsevier B.V. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aged
-
Aged, 80 and over
-
Cell Line
-
Choroid / metabolism
-
Copper / metabolism*
-
Copper / pharmacology
-
Copper Transporter 1 / metabolism
-
DNA-Binding Proteins / metabolism
-
Electron Transport Complex IV / metabolism
-
Epithelial Cells / metabolism*
-
Female
-
Gene Expression Regulation / drug effects
-
Humans
-
Macular Degeneration / metabolism*
-
Macular Degeneration / pathology
-
Male
-
Mitochondria / genetics
-
Mitochondria / metabolism*
-
Mitochondrial Proteins / metabolism
-
Molecular Chaperones / metabolism
-
NF-E2-Related Factor 2 / metabolism
-
Organelle Biogenesis*
-
RNA, Messenger / metabolism
-
RNA-Binding Proteins / metabolism
-
Reactive Oxygen Species / metabolism
-
Retinal Pigment Epithelium / metabolism*
-
Retinal Pigment Epithelium / pathology
-
Retinal Pigments / genetics
-
Retinal Pigments / metabolism*
-
Transcription Factors / metabolism
Substances
-
Copper Transporter 1
-
DNA-Binding Proteins
-
Mitochondrial Proteins
-
Molecular Chaperones
-
NF-E2-Related Factor 2
-
NFE2L2 protein, human
-
PPARGC1B protein, human
-
RNA, Messenger
-
RNA-Binding Proteins
-
Reactive Oxygen Species
-
Retinal Pigments
-
SCO1 protein, human
-
SLC31A1 protein, human
-
TFAM protein, human
-
Transcription Factors
-
Copper
-
Electron Transport Complex IV