Live-cell imaging: new avenues to investigate retinal regeneration.

Live-cell imaging: new avenues to investigate retinal regeneration.
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DOI:
10.4103/1673-5374.213533
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发表时间:
2017-08
影响因子:
6.1
通讯作者:
Hyde DR
Hyde DR
中科院分区:
医学2区
文献类型:
--
作者:
Lahne M;Hyde DR

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感知和响应我们的环境需要功能性神经元协同行动。由退行性疾病引起的神经元细胞损失在人类中不能被替代,导致整合和/或响应感觉线索的功能障碍。相反,斑马鱼(Danio rerio)具有再生失去的神经元的内源性能力。在这里,我们将重点关注导致斑马鱼视网膜神经元再生的过程。死亡的视网膜神经元释放出一种损伤信号,即肿瘤坏死因子α,它诱导驻留的放射状胶质细胞(Müller胶质细胞)重新编程并重新进入细胞周期。Müller胶质细胞不对称分裂,产生退出细胞周期的Müller胶质细胞和神经元祖细胞。出现的神经元祖细胞在迁移到损伤部位以分化成丢失的神经元细胞类型之前经历几轮细胞分裂。分子和免疫组织化学研究主要提供了对调节视网膜再生的机制的了解。然而,视网膜再生过程中的许多过程是动态的,需要活细胞成像来充分识别潜在的机制。最近,成年斑马鱼视网膜培养的多光子成像方法被开发出来。我们将讨论活细胞成像的使用,目前可用的工具和那些需要开发,以提高我们在视网膜再生领域的主要开放问题的知识。
Sensing and responding to our environment requires functional neurons that act in concert. Neuronal cell loss resulting from degenerative diseases cannot be replaced in humans, causing a functional impairment to integrate and/or respond to sensory cues. In contrast, zebrafish (Danio rerio) possess an endogenous capacity to regenerate lost neurons. Here, we will focus on the processes that lead to neuronal regeneration in the zebrafish retina. Dying retinal neurons release a damage signal, tumor necrosis factor α, which induces the resident radial glia, the Müller glia, to reprogram and re-enter the cell cycle. The Müller glia divide asymmetrically to produce a Müller glia that exits the cell cycle and a neuronal progenitor cell. The arising neuronal progenitor cells undergo several rounds of cell divisions before they migrate to the site of damage to differentiate into the neuronal cell types that were lost. Molecular and immunohistochemical studies have predominantly provided insight into the mechanisms that regulate retinal regeneration. However, many processes during retinal regeneration are dynamic and require live-cell imaging to fully discern the underlying mechanisms. Recently, a multiphoton imaging approach of adult zebrafish retinal cultures was developed. We will discuss the use of live-cell imaging, the currently available tools and those that need to be developed to advance our knowledge on major open questions in the field of retinal regeneration.
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