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在视网膜变性的非洲爪蟾模型中 Müller 胶质细胞的再激活。

Müller glial cell reactivation in Xenopus models of retinal degeneration.

机构信息

Paris-Saclay Institute of Neuroscience, CNRS, Univ Paris Sud, Université Paris-Saclay, Orsay, 91405, France.

Centre d'Etude et de Recherche Thérapeutique en Ophtalmologie, Retina France, Orsay, 91405, France.

出版信息

Glia. 2017 Aug;65(8):1333-1349. doi: 10.1002/glia.23165. Epub 2017 May 26.

Abstract

A striking aspect of tissue regeneration is its uneven distribution among different animal classes, both in terms of modalities and efficiency. The retina does not escape the rule, exhibiting extraordinary self-repair properties in anamniote species but extremely limited ones in mammals. Among cellular sources prone to contribute to retinal regeneration are Müller glial cells, which in teleosts have been known for a decade to re-acquire a stem/progenitor state and regenerate retinal neurons following injury. As their regenerative potential was hitherto unexplored in amphibians, we tackled this issue using two Xenopus retinal injury paradigms we implemented: a mechanical needle poke injury and a transgenic model allowing for conditional photoreceptor cell ablation. These models revealed that Müller cells are indeed able to proliferate and replace lost cells following damage/degeneration in the retina. Interestingly, the extent of cell cycle re-entry appears dependent on the age of the animal, with a refractory period in early tadpole stages. Our findings pave the way for future studies aimed at identifying the molecular cues that either sustain or constrain the recruitment of Müller glia, an issue of utmost importance to set up therapeutic strategies for eye regenerative medicine.

摘要

组织再生的一个显著特点是,它在不同的动物类群之间分布不均,无论是在形式还是效率方面。视网膜也不例外,在无羊膜动物物种中表现出非凡的自我修复特性,但在哺乳动物中却极其有限。在易于促进视网膜再生的细胞来源中,Müller 胶质细胞是其中之一,十年来人们已经知道,硬骨鱼中的 Müller 胶质细胞可以重新获得干细胞/祖细胞状态,并在受到损伤后再生视网膜神经元。由于它们在两栖动物中的再生潜力尚未被探索,我们使用我们实施的两种非洲爪蟾视网膜损伤模型来解决这个问题:机械针刺损伤和允许条件性光感受器细胞消融的转基因模型。这些模型表明,Müller 细胞确实能够在视网膜损伤/退化后增殖并替代丢失的细胞。有趣的是,细胞周期重新进入的程度似乎取决于动物的年龄,在早期蝌蚪阶段存在一个不应期。我们的发现为未来的研究铺平了道路,这些研究旨在确定维持或限制 Müller 胶质细胞募集的分子线索,这对于制定眼再生医学的治疗策略至关重要。

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