Context-dependent effects of inflammation on retina regeneration
Context-dependent effects of inflammation on retina regeneration
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DOI：
10.1007/s12035-022-02857-9
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发表时间：
2021-10
影响因子：
5.1
通讯作者：
Cuiping Zhou;Xiaoli Zhang;Yuxi Chen;Zi-hao Lin;Shuqiang Zhang;Zhiqiang Zhang;Li-ning Cao;H. Guan;Jianfeng Lu;Hui Xu
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文献类型：
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作者：
Cuiping Zhou;Xiaoli Zhang;Yuxi Chen;Zi-hao Lin;Shuqiang Zhang;Zhiqiang Zhang;Li-ning Cao;H. Guan;Jianfeng Lu;Hui Xu
在受伤的鱼类和鸟类视网膜中，穆勒胶质细胞（MG）增殖成多能祖细胞（MGPC）需要炎症。然而，其在视网膜再生中的功能尚未完全了解。在这里，我们研究了炎症在斑马鱼三种不同视网膜再生模式（刺伤、NMDA 损伤和胰岛素治疗）中的作用。我们首先表明，在这些范例的视网膜中发现了不同类型的免疫细胞和炎症细胞因子水平。尽管单独注射酵母聚糖不足以诱导未受伤视网膜中的 MG 增殖，但免疫抑制显着抑制了所有三种范例中 MGPC 的形成。刺伤后炎症的增强促进了 MGPC 的形成，同时在 NMDA 或胰岛素模型中表现出环境依赖性作用。我们进一步表明，适当水平的炎症促进刺伤或 NMDA 损伤后 MG 重编程和细胞周期重新进入，但在后一种模型中，过度炎症也会抑制 MG 增殖。最后，炎症对各种损伤范例中的神经元再生有不同的影响。我们的研究揭示了鱼类视网膜修复过程中炎症的复杂且依赖于环境的作用，并表明准确的炎症管理可能对于哺乳动物视网膜成功再生至关重要。
Inflammation is required for the proliferation of Müller glia (MG) into multipotent progenitors (MGPCs) in the injured fish and avian retinas. However, its function in retina regeneration has not been fully understood. Here we investigated the role of inflammation in three different retinal regeneration paradigms in zebrafish (stab-injury, NMDA-injury and insulin treatment). We first show that different types of immune cells and levels of inflammatory cytokines were found in the retinas of these paradigms. Though zymosan injection alone was insufficient to induce MG proliferation in the uninjured retina, immune suppression significantly inhibited MGPC formation in all three paradigms. Enhancing inflammation promoted MGPC formation after stab-injury, while exhibiting a context-dependent role in the NMDA or insulin models. We further show that proper levels of inflammation promoted MG reprogramming and cell cycle re-entry after stab- or NMDA-injury, but excessive inflammation also suppressed MG proliferation in the latter model. Finally, inflammation differentially affected neuronal regeneration in various injury paradigms. Our study reveals the complex and context-dependent role of inflammation during retinal repair in fish and suggests accurate inflammation management may be crucial for successful retina regeneration in mammals.