药理性纤维细胞重新编程到光受体恢复视力
Biraj Mahato1, Koray Dogan Kaya2, Yan Fan1
1Department of Pharmacology and Neuroscience, Laboratory for Retinal Rehabilitation, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, TX, USA.
Nature
|May 8, 2020
概括
科学家用五种小分子将纤维细胞重新编程成类似光受体的细胞. 这些细胞在患有遗传性视网膜退化症的小鼠中恢复了部分视力,
科学领域:
- 眼科和再生医学
- 细胞重编程和视力恢复
背景情况:
- 由于目前没有恢复视力的治疗方法, 视网膜病变会通过光受体细胞损失导致不可逆转的失明.
- 通过化学重编程从其他细胞类型生成特定的神经元亚型,如光受体,仍然是一个重大挑战.
研究的目的:
- 研究化学重编程的潜力,从纤维细胞中产生功能性的光受体样细胞.
- 在视网膜退化的小鼠模型中评估移植的化学诱导光感应器样细胞 (CiPC) 的治疗效果.
主要方法:
- 用一种由五个小分子组成的特殊尾酒来诱导纤维细胞转化为光受体样细胞.
- 将CiPC移植到缺少Pde6b (rd1) 的小鼠中,这是杆性退化的一个模型.
- 使用瞳孔反射测试评估视觉功能恢复,并评估潜在的分子机制,包括线核通信.
主要成果:
- 成功地将纤维细胞诱导到棒光受体样细胞 (CiPC).
- 在rd1小鼠中,移植CiPC使瞳孔反射和视觉功能部分恢复.
- 确定了核通信,包括AXIN2转移到线粒体,反应性氧物种的产生,NF-κB激活和Ascl1上调,对于CiPC产生至关重要.
结论:
- 化学重编程为产生光受体样细胞提供了一个可行的策略.
- 在遗传性视网膜疾病模型中,CiPC显示了视力恢复的治疗潜力.
- 了解细胞核沟通通路是治疗失明的关键.
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