Department of Anatomy and Cell Biology, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA.
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA; Department of Ophthalmology, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA.
Exp Eye Res. 2018 Jan;166:106-115. doi: 10.1016/j.exer.2017.10.003. Epub 2017 Oct 10.
In contrast to the mammalian retina, the zebrafish retina possesses the ability to regenerate. This is primarily accomplished through Müller glial cells, which, upon damage, re-enter the cell cycle to form retinal progenitors. The progenitors continue to proliferate as they migrate to the area of damage and ultimately differentiate into new neurons. The purpose of this study was to characterize the expression and function of Sonic Hedgehog (Shh) during regeneration of the adult zebrafish retina. Expression profiling of Shh pathway genes showed a significant upregulation of expression associated with stages of progenitor proliferation and neuronal differentiation. Activation of Shh signaling during early stages of retinal regeneration using intraocular injections of the recombinant human SHH (SHH-N) resulted in increased Müller cell gliosis, proliferation, and neuroprotection of damaged retinal neurons. Continued activation of Shh resulted in a greater number of differentiated amacrine and ganglion cells in the fully regenerated retina. Conversely, inhibition of Shh signaling using intraocular injections of cyclopamine resulted in decreased Müller glial cell proliferation and a fewer number of regenerated amacrine and ganglion cells. These data suggest that Shh signaling plays pleiotropic roles in proliferation and differentiation during adult zebrafish retinal regeneration.
与哺乳动物的视网膜不同，斑马鱼的视网膜具有再生能力。这主要是通过 Müller 胶质细胞实现的，这些细胞在受到损伤后重新进入细胞周期，形成视网膜祖细胞。祖细胞在迁移到损伤区域的过程中继续增殖，并最终分化为新的神经元。本研究的目的是描述 Sonic Hedgehog（Shh）在成年斑马鱼视网膜再生过程中的表达和功能。Shh 通路基因的表达谱分析显示，与祖细胞增殖和神经元分化阶段相关的表达显著上调。通过眼内注射重组人 SHH（SHH-N）在视网膜再生的早期激活 Shh 信号，导致 Müller 胶质细胞增生、增殖，并对受损的视网膜神经元起到神经保护作用。持续激活 Shh 导致完全再生的视网膜中分化的无长突细胞和节细胞数量增加。相反，通过眼内注射环巴胺抑制 Shh 信号，导致 Müller 胶质细胞增殖减少，再生的无长突细胞和节细胞数量减少。这些数据表明，Shh 信号在成年斑马鱼视网膜再生过程中的增殖和分化中发挥多种作用。
