Bludau Oliver, Weber Anke, Bosak Viktoria, Kuscha Veronika, Dietrich Kristin, Hans Stefan, Brand Michael
CRTD-Center for Regenerative Therapies, and PoL-Cluster of Excellence Physics of Life, Dresden, Germany.
Front Cell Dev Biol. 2024 Jul 12;12:1332347. doi: 10.3389/fcell.2024.1332347. eCollection 2024.
Inflammation can lead to persistent and irreversible loss of retinal neurons and photoreceptors in mammalian vertebrates. In contrast, in the adult zebrafish brain, acute neural inflammation is both necessary and sufficient to stimulate regeneration of neurons. Here, we report on the critical, positive role of the immune system to support retina regeneration in adult zebrafish. After sterile ablation of photoreceptors by phototoxicity, we find rapid response of immune cells, especially monocytes/microglia and neutrophils, which returns to homeostatic levels within 14 days post lesion. Pharmacological or genetic impairment of the immune system results in a reduced Müller glia stem cell response, seen as decreased reactive proliferation, and a strikingly reduced number of regenerated cells from them, including photoreceptors. Conversely, injection of the immune stimulators flagellin, zymosan, or M-CSF into the vitreous of the eye, leads to a robust proliferation response and the upregulation of regeneration-associated marker genes in Müller glia. Our results suggest that neuroinflammation is a necessary and sufficient driver for retinal regeneration in the adult zebrafish retina.
在哺乳动物脊椎动物中，炎症可导致视网膜神经元和光感受器持续且不可逆的损失。相比之下，在成年斑马鱼大脑中，急性神经炎症对于刺激神经元再生既是必要的也是充分的。在此，我们报告了免疫系统在支持成年斑马鱼视网膜再生方面的关键积极作用。在用光毒性对光感受器进行无菌消融后，我们发现免疫细胞，尤其是单核细胞/小胶质细胞和中性粒细胞会迅速做出反应，损伤后14天内会恢复到稳态水平。免疫系统的药理学或基因损伤会导致穆勒胶质干细胞反应减弱，表现为反应性增殖减少，并且从它们再生的细胞数量显著减少，包括光感受器。相反，向眼玻璃体内注射免疫刺激剂鞭毛蛋白、酵母聚糖或巨噬细胞集落刺激因子（M-CSF），会导致穆勒胶质细胞产生强烈的增殖反应，并上调与再生相关的标记基因。我们的结果表明，神经炎症是成年斑马鱼视网膜再生的必要且充分驱动因素。
