Galectin-3 Promotes Müller Glia Clearance Phagocytosis via MERTK and Reduces Harmful Müller Glia Activation in Inherited and Induced Retinal Degeneration.
Galectin-3 Promotes Müller Glia Clearance Phagocytosis via MERTK and Reduces Harmful Müller Glia Activation in Inherited and Induced Retinal Degeneration.
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半乳糖凝集素-3通过MERTK促进神经胶质细胞清除吞噬，并减少遗传和诱导视网膜变性中有害的神经胶质细胞激活。
DOI：
10.3389/fncel.2022.878260
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发表时间：
2022
影响因子：
5.3
通讯作者：
Finnemann, Silvia C.
中科院分区：
文献类型：
--
作者：
Lew, Deborah S.;McGrath, Morgan J.;Finnemann, Silvia C.
清除吞噬作用是视网膜内神经胶质细胞的一种已知功能。然而，神经胶质瘤吞噬的分子机制在很大程度上仍然不清楚。在这里，我们发现细胞外半乳糖凝集素-3和蛋白S以一种可添加、可饱和的方式促进永生化人io - m1 m<e:1>细胞的清除吞噬作用。半乳糖凝集素-3促进野生型（WT）小鼠初级神经胶质细胞的吞噬作用，但对缺乏吞噬受体MERTK并因此发生出生后光感受器变性的小鼠则没有作用。研究人员发现，MERTK - / - m<s:1> ller胶质细胞在出生后20天（P20）显示出过量的半乳糖凝集素-3，这是在可检测到的光感受器变性之前的年龄。此外，与单独缺乏MERTK的小鼠相比，缺乏半乳糖凝集素-3和MERTK的双敲除（DKO）小鼠在P20时显示出更大的<s:1> ller细胞激活（而不是小胶质细胞），P35时更明显的光感受器丧失。在完善的碘酸钠损伤模型中，我们还发现，与WT小鼠相比，缺乏半乳糖凝集素-3的小鼠的神经胶质细胞特异性激活更严重，视网膜损伤更严重。事实上，半乳糖凝集素-3缺乏显著增加了对损伤的敏感性，在碘酸钠浓度下产生<s:1> ller激活和视网膜损伤，而对WT视网膜没有影响。总之，我们从遗传和急性诱导的视网膜变性模型得出的结果一致认为，消除半乳糖凝集素-3会加剧<s:1> ller细胞活化和视网膜变性。这些数据确定了MERTK配体半乳糖凝集素-3在视网膜中抑制<s:1> ller胶质细胞激活的重要保护作用。
Clearance phagocytosis is a documented function of Müller glia in the retina. However, the molecular mechanisms of Müller glia phagocytosis remain largely undefined. Here, we show that extracellular galectin-3 and protein S promote clearance phagocytosis by immortalized human MIO-M1 Müller cells in an additive, saturable manner. Galectin-3 promotes phagocytosis by primary Müller glia from wild-type (WT) mice but not from mice that lack the engulfment receptor MERTK and therefore develop postnatal photoreceptor degeneration. Probing a possible functional link between Müller galectin-3 and MERTK, we discovered that mertk−/− Müller glia in situ show excess galectin-3 at postnatal day 20 (P20), an age prior to detectable photoreceptor degeneration. Moreover, double knockout (DKO) mice lacking both galectin-3 and MERTK show increased activation of Müller cells (but not of microglia) at P20 and more pronounced photoreceptor loss at P35 compared to mice lacking MERTK alone. Exploring the well-established sodium iodate injury model, we also found more severe activation specifically of Müller glia, and worse retinal damage in mice lacking galectin-3 compared to WT mice. Indeed, galectin-3 deficiency significantly increased sensitivity to injury, yielding Müller activation and retinal damage at a sodium iodate concentration that had no effect on the WT retina. Altogether, our results from both inherited and acutely induced models of retinal degeneration agree that eliminating galectin-3 exacerbates Müller cell activation and retinal degeneration. These data identify an important protective role for the MERTK ligand galectin-3 in the retina in restraining Müller glia activation.
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影响因子：
3.7
作者：
Bauer PM;Zalis MC;Abdshill H;Deierborg T;Johansson F;Englund-Johansson U
通讯作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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影响因子：
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作者：
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通讯作者：
Finnemann, Silvia C.
影响因子：
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作者：
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影响因子：
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作者：
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