Role of microglia during retinal neurogenesis

描述(申请人提供)：正常的视觉功能取决于在发育过程中视网膜细胞类型的平衡补充。虽然人们对视网膜祖细胞的增殖和分化已经有了很多了解，但对于小胶质细胞是如何调控这种增殖和分化的，人们却知之甚少。小胶质细胞是中枢神经系统的常驻神经免疫细胞。小胶质细胞在眼睛发育的早期就渗透到小鼠视网膜，并在e11.5出现，这与视网膜神经发生的开始是一致的。然而，尽管小胶质细胞在神经发生的最早阶段普遍存在，并提示在皮质神经发生中发挥作用，但我们缺乏对这些细胞是否调节前体细胞的生存、增殖或分化的详细了解，特别是在发育中的视网膜。在这里，我们建议定义小胶质细胞在视网膜发育过程中的分布、激活和基因表达变化的模式，首先通过对多个阶段的GFP标记的小胶质细胞进行成像，然后通过在发育过程中生成小胶质细胞的全面分子图谱。接下来，我们将测试抑制或消除小胶质细胞是否会改变视网膜前体细胞的增殖、存活或分化。这项研究将提供胚胎眼发育过程中小胶质细胞功能的详细研究，并将阐明神经免疫相互作用在视觉系统发育中的作用。

DESCRIPTION (provided by applicant): Normal visual function depends upon the generation of a balanced complement of retinal cell types during development. Although much has been learned about retinal progenitor proliferation and differentiation, little is known about how this s modulated by microglia, which is the resident neuroimmune cell of the central nervous system (CNS). Microglia infiltrates the mouse retina at early stages of eye development and is present by e11.5 coincident with the onset of retinal neurogenesis. However, despite the prevalence of microglia at the earliest stages of neurogenesis and suggestive evidence for a role in cortical neurogenesis, we lack a detailed understanding of whether these cells regulate progenitor cell survival, proliferation or differentiation, particularly in the developing retina. Here we propose o define the pattern of microglia distribution, activation and gene expression changes during retinal development, first by imaging GFP labeled microglia at multiple stages, and then by generating a comprehensive molecular profile of microglia over developmental time. Next we will test whether inhibiting or eliminating microglia alters retinal progenitor proliferation, survval or differentiation. This study will provide a detailed investigation of microglia function during embryonic eye development, and will shed light on the role of neuro-immune interactions on visual system development.