Role of microglia during retinal neurogenesis

描述（由申请人提供）：正常的视觉功能取决于在发育过程中视网膜细胞类型平衡补充的产生。虽然已经了解了很多关于视网膜祖细胞的增殖和分化，很少有人知道这是如何调节的小胶质细胞，这是常驻中枢神经系统（CNS）的神经免疫细胞。小胶质细胞在眼睛发育的早期阶段浸润小鼠视网膜，并在e11.5出现，与视网膜神经发生的开始一致。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起作用的证据，我们缺乏对这些细胞是否调节祖细胞存活、增殖或分化的详细了解，特别是在发育中的视网膜中。在这里，我们提出o定义的模式，视网膜发育过程中的小胶质细胞的分布，激活和基因表达的变化，首先通过成像GFP标记的小胶质细胞在多个阶段，然后通过生成一个全面的小胶质细胞在发育时间的分子概况。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祖细胞的增殖、存活或分化。这项研究将详细研究胚胎眼睛发育期间小胶质细胞的功能，并揭示神经免疫相互作用对视觉系统发育的作用。

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.