R S Mehta Jain Department of Biochemistry and Cell Biology, KBIRVO, Vision Research Foundation, Sankara Nethralaya, College Road, Nungambakkam, Chennai - 6, India; SASTRA deemed to be University, Trichy - Tanjore Road, Thirumalaisamudram, Thanjavur, Tamil Nadu 613401, India.
R S Mehta Jain Department of Biochemistry and Cell Biology, KBIRVO, Vision Research Foundation, Sankara Nethralaya, College Road, Nungambakkam, Chennai - 6, India.
Biochim Biophys Acta Mol Basis Dis. 2020 Oct 1;1866(10):165843. doi: 10.1016/j.bbadis.2020.165843. Epub 2020 May 23.
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.
年龄相关性黄斑变性（AMD）是一种多因素疾病，具有遗传、生化和环境风险因素。我们观察到 AMD 供体眼球脉络膜-RPE 中的铜水平显著升高。体外暴露于铜的成年视网膜色素上皮细胞（ARPE19 细胞）在 50 μM 浓度下铜内流转运蛋白 CTR1 和铜摄取增加了 2 倍。此外，铜处理后细胞色素 C 氧化酶活性增加了 2 倍，NRF2 的 mRNA 表达增加了 2 倍。线粒体生物发生标志物 PGC1β 和 TFAM 的表达显著增加，这可以通过线粒体质量和拷贝数得到证实。相反，在 AMD 脉络膜-RPE 中，与相应的对照相比，CTR1 mRNA 明显下调。SCO1 和 PGC1β mRNA 在脉络膜-RPE 中增加。我们的研究表明铜在 RPE 细胞中线粒体生物发生中发挥重要作用。
