Galectin-3 Mediates TGF-β-Controlled Migration in Müller Glial Cells

Galectin-3 (Gal-3) is a ß-galactoside sugar-binding protein increasingly recognised for its role in systemic inflammation, fibrosis, and cancer. Within the retina, Müller glial cells (MGCs) are a major producer of Gal-3. This study aimed to investigate the impact of Gal-3 on the migration of MGCs. CRISPR-Cas9 knockout of Gal-3 resulted in slower cellular migration in MGCs (p < 0.001). This was partially rescued by the addition of exogenous Gal-3 (p < 0.01). The addition of Gal-3 inhibitor TD139 (p < 0.01) resulted in decreased cellular migration, whilst the addition of Neuraminidase 1 (p < 0.05) resulted in increased cellular migration. TGF-β treatment downregulated Gal-3 mRNA (p < 0.01) and protein (p < 0.001) expression; increased the mRNA expression of various sialylation enzymes; and resulted in significantly decreased cellular proliferation (p < 0.01) and migration (p < 0.001). These findings establish Gal-3 as a pro-migratory driver in MGCs under the regulation of TGF-β. Consequently, targeting the Gal-3/tissue sialylation axis represents a promising therapeutic avenue for mitigating pathological glial proliferation and migration in conditions such as proliferative vitreoretinopathy.