| First Author | Lew DS | Year | 2022 |
| Journal | Front Cell Neurosci | Volume | 16 |
| Pages | 878260 | PubMed ID | 35711472 |
| Mgi Jnum | J:326106 | Mgi Id | MGI:7293457 |
| Doi | 10.3389/fncel.2022.878260 | Citation | Lew DS, et al. (2022) Galectin-3 Promotes Muller Glia Clearance Phagocytosis via MERTK and Reduces Harmful Muller Glia Activation in Inherited and Induced Retinal Degeneration. Front Cell Neurosci 16:878260 |
| abstractText | 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. |
