Department of Ophthalmology and Visual Science, University of Nebraska Medical Center, Omaha, NE, USA.
Department of Ophthalmology and Visual Science, University of Nebraska Medical Center, Omaha, NE, USA.
Stem Cell Reports. 2024 Aug 13;19(8):1092-1106. doi: 10.1016/j.stemcr.2024.06.009. Epub 2024 Jul 25.
Microglia (μG), the resident immune cells in the central nervous system, surveil the parenchyma to maintain the structural and functional homeostasis of neurons. Besides, they influence neurogenesis and synaptogenesis through complement-mediated phagocytosis. Emerging evidence suggests that μG may also influence development through proinflammatory cytokines. Here, we examined the premise that tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), the two most prominent components of the μG secretome, influence retinal development, specifically the morphological and functional differentiation of human retinal ganglion cells (hRGCs). Using controlled generation of hRGCs and human μG (hμG) from pluripotent stem cells, we demonstrate that TNF-α and IL-1β secreted by unchallenged hμG did not influence hRGC generation. However, their presence significantly facilitated neuritogenesis along with the basal function of hRGCs, which involved the recruitment of the AKT/mTOR pathway. We present ex vivo evidence that proinflammatory cytokines may play an important role in the morphological and physiological maturation of hRGCs, which may be recapitulated for regeneration.
小胶质细胞（μG）是中枢神经系统中的固有免疫细胞，监测实质以维持神经元的结构和功能平衡。此外，它们还通过补体介导的吞噬作用影响神经发生和突触发生。新出现的证据表明，μG 也可能通过促炎细胞因子影响发育。在这里，我们研究了肿瘤坏死因子 α（TNF-α）和白细胞介素 1β（IL-1β）这两种μG 分泌组中最突出的成分是否影响视网膜发育，特别是人视网膜神经节细胞（hRGC）的形态和功能分化的前提。我们使用多能干细胞有控制地生成 hRGC 和人 μG（hμG），证明未受挑战的 hμG 分泌的 TNF-α 和 IL-1β 不会影响 hRGC 的生成。然而，它们的存在显著促进了 hRGC 的神经突形成以及其基本功能，这涉及 AKT/mTOR 途径的募集。我们提出了体外证据，表明促炎细胞因子可能在 hRGC 的形态和生理成熟中发挥重要作用，这可能会被重新用于再生。
