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重编程 Müller 胶质细胞以再生视网膜神经元。

Reprogramming Müller Glia to Regenerate Retinal Neurons.

机构信息

Center for Zebrafish Research, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556, USA; email:

Center for Stem Cells and Regenerative Medicine, University of Notre Dame, Notre Dame, Indiana 46556, USA.

出版信息

Annu Rev Vis Sci. 2020 Sep 15;6:171-193. doi: 10.1146/annurev-vision-121219-081808. Epub 2020 Apr 28.

Abstract

In humans, various genetic defects or age-related diseases, such as diabetic retinopathies, glaucoma, and macular degeneration, cause the death of retinal neurons and profound vision loss. One approach to treating these diseases is to utilize stem and progenitor cells to replace neurons in situ, with the expectation that new neurons will create new synaptic circuits or integrate into existing ones. Reprogramming non-neuronal cells in vivo into stem or progenitor cells is one strategy for replacing lost neurons. Zebrafish have become a valuable model for investigating cellular reprogramming and retinal regeneration. This review summarizes our current knowledge regarding spontaneous reprogramming of Müller glia in zebrafish and compares this knowledge to research efforts directed toward reprogramming Müller glia in mammals. Intensive research using these animal models has revealed shared molecular mechanisms that make Müller glia attractive targets for cellular reprogramming and highlighted the potential for curing degenerative retinal diseases from intrinsic cellular sources.

摘要

在人类中,各种遗传缺陷或与年龄相关的疾病,如糖尿病性视网膜病变、青光眼和黄斑变性,会导致视网膜神经元死亡和严重的视力丧失。治疗这些疾病的一种方法是利用干细胞和祖细胞原位替代神经元,期望新的神经元会创建新的突触回路或整合到现有的回路中。将体内的非神经元细胞重编程为干细胞或祖细胞是替代丢失神经元的一种策略。斑马鱼已成为研究细胞重编程和视网膜再生的有价值的模型。这篇综述总结了我们目前对斑马鱼中 Müller 胶质细胞自发重编程的认识,并将这些知识与针对哺乳动物中 Müller 胶质细胞重编程的研究工作进行了比较。使用这些动物模型的深入研究揭示了共享的分子机制,使 Müller 胶质细胞成为细胞重编程的有吸引力的靶标,并强调了从内在细胞来源治疗退行性视网膜疾病的潜力。

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