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.

中文翻译：

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Atp7b 缺陷会导致斑马鱼眼睛发育缺陷。

作为一种铜 (Cu) 转运 ATP 酶，ATP7B 在维持体内铜稳态方面起着重要作用，其功能障碍与视网膜疾病有关。然而，ATP7B 功能障碍和随后的铜超载如何引起视网膜损伤尚不清楚。在这里，我们表明 atp7b-/- 纯合子斑马鱼幼虫对光刺激不敏感，视网膜细胞减少但形态表型正常。此外，在 atp7b-/- 突变的幼虫中揭示了一系列差异表达的基因，这些基因丰富了光转导、晶状体的结构成分、光刺激的感官知觉、氧化磷酸化和 ATP 酶活性。此外，我们还展示了 atp7b-/- 突变幼虫视网膜细胞中铜的积累，这会导致内质网 (ER) 应激和视网膜细胞凋亡以及随后的视网膜缺陷。本研究中的整体数据表明，atp7b 突变导致铜在斑马鱼视网膜细胞中积累，并导致 ER 应激和视网膜细胞死亡。这些数据可能对解释ATP7B突变的铜失调综合征Wilson病中发生的视网膜疾病提供了一些可能的提示。