Mueller glia activation by VEGF-antagonizing drugs: An in vitro study on rat primary retinal cultures

The effects of the anti-Vascular Endothelial Growth Factor (VEGF) drugs ranibizumab and aflibercept were studied in Mueller glia in primary mixed cultures from rat neonatal retina. Treatment with both agents induced activation of Mueller glia, demonstrated by increased levels of Glial Fibrillary Acidic Protein. In addition, phosphorylated Extracellular-Regulated Kinase 1/2 (ERK 1/2) showed enhanced immunoreactivity in activated Mueller glia. Treatment with aflibercept induced an increase in K super(+) channel (Kir) 4.1 levels and both drugs upregulated Aquaporin 4 (AQP4) in activated Mueller glia. The results show that VEGF-antagonizing drugs influence the homeostasis of Mueller cells in primary retinal cultures, inducing an activated phenotype. Upregulation of Kir4.1 and AQP4 suggests that Mueller glia activation following anti-VEGF drugs may not depict a detrimental gliotic reaction. Indeed, it could represent one of the mechanisms able to contribute to the therapeutic effects of these drugs, particularly in the presence of macular edema.