斑马鱼
视网膜
生物
细胞生物学
内质网
视网膜变性
未折叠蛋白反应
遗传学
生物化学
基因
作者
You Wu,Wenye Liu,LingYa Li,Zhipeng Tai,Baoxiang Gao,Jing‐Xia Liu
出处
期刊:Metallomics
[Oxford University Press]
日期:2023-04-18
卷期号:15 (5)
被引量:2
标识
DOI:10.1093/mtomcs/mfad024
摘要
As a copper (Cu) transport ATPase, ATP7B plays an important role in maintaining Cu homeostasis in the body and its dysfunction is associated with retinal disease. How ATP7B dysfunction and the subsequent Cu overload induce retinal damage, however, are unknown. Here, we show that atp7b-/- homozygous zebrafish larvae are insensitive to light stimulation, with a reduction in retinal cells but normal like morphological phenotypes. Additionally, a series of differentially expressed genes are unveiled in atp7b-/- mutated larvae, which enrich in photo-transduction, structural constituent of eye lens, sensory perception of light stimulus, oxidative phosphorylation, and ATPase activity. Moreover, we show the Cu accumulation in retinal cells in atp7b-/- mutated larvae, which results in endoplasmic reticulum (ER) stress and retinal cell apoptosis and subsequent retinal defects. The integral data in this study demonstrate that atp7b mutation leads to Cu accumulation in zebrafish retinal cells and the consequence ER stress and retinal cell death. These data may give some possible hints to explain retinal disease occurred in the Cu dysregulation syndromes Wilson's disease with ATP7B mutation.
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