Lahne Manuela, Hyde David R
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA.
Neural Regen Res. 2017 Aug;12(8):1210-1219. doi: 10.4103/1673-5374.213533.
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 () 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.
感知和响应我们的环境需要协同作用的功能性神经元。人类因退行性疾病导致的神经元细胞损失无法得到替代，从而造成整合和/或响应感觉线索的功能障碍。相比之下，斑马鱼具有再生丢失神经元的内在能力。在这里，我们将聚焦于斑马鱼视网膜中导致神经元再生的过程。濒死的视网膜神经元会释放一种损伤信号——肿瘤坏死因子α，它会诱导视网膜中的常驻放射状胶质细胞，即穆勒胶质细胞，进行重编程并重新进入细胞周期。穆勒胶质细胞不对称分裂，产生一个退出细胞周期的穆勒胶质细胞和一个神经祖细胞。产生的神经祖细胞在迁移到损伤部位分化为丢失的神经元细胞类型之前会经历几轮细胞分裂。分子和免疫组织化学研究主要为调节视网膜再生的机制提供了见解。然而，视网膜再生过程中的许多过程是动态的，需要活细胞成像才能全面了解其潜在机制。最近，一种针对成年斑马鱼视网膜培养物的多光子成像方法被开发出来。我们将讨论活细胞成像的应用、当前可用的工具以及为推进我们对视网膜再生领域主要未解决问题的认识而需要开发的工具。
