Chunyan Liao, Shuai Chen, Xuxu Chen, Wanying Yi, Yingying Fan, Yuewen Chen, Tao Ye, Yu Chen
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引用次数: 0
摘要
视网膜色素变性(RP)是一种遗传性眼病,会导致进行性视力丧失。小胶质细胞活化和炎症在视网膜色素变性的光感受器变性过程中起着至关重要的作用,但其潜在机制仍不清楚。在这里,我们研究了 RP 小鼠模型 rd1 小鼠光感受器的进行性退化。我们利用单细胞 RNA 测序技术研究了 rd1 小鼠各种视网膜细胞的分子变化,发现 JNK 信号的增强与 RP 中的光感受器退化有关。此外,JNK 下游的炎症相关分子在 RP 中升高。此外,抑制 JNK 可减轻小胶质细胞的活化,并挽救 rd1 小鼠的感光细胞变性。因此,我们的研究结果表明,以 JNK 为靶点是减缓 RP 进展的一种可行方法。
Inhibition of JNK ameliorates rod photoreceptor degeneration in a mouse model of retinitis pigmentosa
Retinitis pigmentosa (RP) is an inherited eye disease that causes progressive vision loss. Microglial activation and inflammation play essential roles in photoreceptor degeneration in RP, although the underlying mechanisms remain unclear. Here, we examined the progressive degeneration of photoreceptors in rd1 mice, a mouse model of RP. We investigated the molecular changes in various retinal cells in rd1 mice using single-cell RNA sequencing and found that potentiation of JNK signaling is associated with photoreceptor degeneration in RP. Moreover, inflammation-related molecules, which function downstream of JNK, are elevated in RP. Furthermore, inhibiting JNK alleviates microglial activation and rescues photoreceptor degeneration in rd1 mice. Thus, our findings suggest that targeting JNK is a promising approach for slowing RP progression.
期刊介绍:
FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.