中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (12): 1951-1952.doi: 10.4103/1673-5374.165301

• 观点:视神经损伤修复保护与再生 • 上一篇    下一篇

胰岛因子1在视网膜神经发生中的作用?

  

  • 收稿日期:2015-08-29 出版日期:2015-12-30 发布日期:2015-12-30
  • 基金资助:

    这项研究由自西班牙科技部(BFU2007-67540),埃斯特雷马杜拉军政府(GR10152 PRI06A195)资助。

The role of Islet-1 in cell specification, differentiation, and maintenance of phenotypes in the vertebrate
neural retina

Gervasio Martín-Partido, Javier Francisco-Morcillo*   

  1. Departamento de Biología Celular, Facultad de Ciencias, Universidad de Extremadura, Badajoz, Spain
  • Received:2015-08-29 Online:2015-12-30 Published:2015-12-30
  • Contact: Javier Francisco-Morcillo, Ph.D., morcillo@unex.es.
  • Supported by:

    This work was supported by grants from the Spanish Ministerio de Ciencia y Tecnología (BFU2007-67540), and the Junta de Extremadura (PRI06A195; GR10152).

摘要:

许多致盲疾病,如视网膜色素变性,老年性黄斑变性和青光眼都与视网膜神经细胞、光感受器尤其是中央投影视网膜神经节细胞的永久损失有关。在发育视网膜中,一系列复杂的转录因子参与分解序贯激活基因发育。其中,LIM-同源转录因子胰岛-1在发育和成熟神经节胆碱能无长突、ON-双极和水平细胞中有所表达,其相关研究也通常在脊椎动物的视网膜中进行。由于胰岛因子-1突变小鼠会在胚胎期9.5天后死亡,所以在视网膜发生前,胰岛因子-1在视网膜神经发生中作用基本上仍不明确。然而,胰岛因子-1条件性敲除可以生成确定视网膜发育中的确切作用。因此,该转录因子视网膜发生的条件在小鼠视网膜会导致成熟双极,无长突和神经节细胞明显减少,并有伴有大量水平细胞。文章认为胰岛-1似乎在细胞分类,分化和维持视网膜细胞类型表型中具有高度保护作用,胰岛因子-1的这种神经保护作用可被用于重编程移植的视网膜干细胞。

Abstract:

Many blinding diseases, such as retinitis pigmentosa, age-related macular degeneration, and glaucoma involve the permanent loss of retinal neurons, especially photoreceptors or the centrally projecting retinal ganglion cells. Stem cells have been proposed as a potential source of cells for neuronal transplantation, due to their capacity for proliferative expansion and the potential to generate different retinal cell types. Understanding the developmental biology of retinal cells will be the key to the success of such a strategy. In the developing retina, a complex series of transcription factors sequentially activates genes involved in development, thus defining the adult cell type. Among these, the LIM-homeodomain transcription factor Islet-1 (Isl1) is expressed by developing and mature ganglion, cholinergic amacrine, ON-bipolar, and horizontal cells in the retina of most of the vertebrates that have been studied. Because Isl1-null mutant mice die at embryonic day 9.5, before the onset of retinogenesis, the role of Isl1 in retinal neurogenesis remained largely unknown. However, Isl1 conditional knockout has been generated to identify the exact role of Isl1 in retinal development. Thus, the conditional inactivation of this transcription factor during mouse retinogenesis disrupts retinal function and also results in marked reductions in mature bipolar, amacrine, and ganglion cells, and a substantial increase in horizontal cells. Therefore, Isl1 seems to play a highly conserved role in cell specification, differentiation, and maintenance of phenotypes of retinal cell types. An understanding of factors such as Isl1 that are involved in vertebrate retinogenesis might be exploitable to reprogram transplanted retinal stem cells.