Galectin-3 Promotes Müller Glia Clearance Phagocytosis via MERTK and Reduces Harmful Müller Glia Activation in Inherited and Induced Retinal Degeneration

Lew, Deborah S. and McGrath, Morgan J. and Finnemann, Silvia C. (2022) Galectin-3 Promotes Müller Glia Clearance Phagocytosis via MERTK and Reduces Harmful Müller Glia Activation in Inherited and Induced Retinal Degeneration. Frontiers in Cellular Neuroscience, 16. ISSN 1662-5102

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Abstract

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.

Item Type: Article
Subjects: Lib Research Guardians > Medical Science
Depositing User: Unnamed user with email support@lib.researchguardians.com
Date Deposited: 03 Apr 2023 09:28
Last Modified: 13 Aug 2024 06:24
URI: http://eprints.classicrepository.com/id/eprint/622

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