期刊
FRONTIERS IN CELLULAR NEUROSCIENCE
卷 16, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2022.878260
关键词
retina; retinal degeneration; phagocytosis; galectin-3; glia; Muller cells
The research shows that extracellular galectin-3 and protein S can promote clearance phagocytosis by Muller cells, with MERTK receptor playing a role in this process. Lack of galectin-3 leads to increased activation of Muller cells and exacerbation of retinal damage.
Clearance phagocytosis is a documented function of Muller glia in the retina. However, the molecular mechanisms of Muller glia phagocytosis remain largely undefined. Here, we show that extracellular galectin-3 and protein S promote clearance phagocytosis by immortalized human MIO-M1 Muller cells in an additive, saturable manner. Galectin-3 promotes phagocytosis by primary Muller 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 Muller galectin-3 and MERTK, we discovered that mertk(-/-) Muller 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 Muller 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 Muller glia, and worse retinal damage in mice lacking galectin-3 compared to WT mice. Indeed, galectin-3 deficiency significantly increased sensitivity to injury, yielding Muller 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 Muller cell activation and retinal degeneration. These data identify an important protective role for the MERTK ligand galectin-3 in the retina in restraining Muller glia activation.
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