title: Müller glia activation by VEGF-antagonizing drugs: An in vitro study on rat primary retinal cultures.
abstract: The effects of the anti-Vascular Endothelial Growth Factor (VEGF) drugs ranibizumab and aflibercept were studied in Müller glia in primary mixed cultures from rat neonatal retina. Treatment with both agents induced activation of Müller 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 Müller glia. Treatment with aflibercept induced an increase in K(+) channel (Kir) 4.1 levels and both drugs upregulated Aquaporin 4 (AQP4) in activated Müller glia. The results show that VEGF-antagonizing drugs influence the homeostasis of Müller cells in primary retinal cultures, inducing an activated phenotype. Upregulation of Kir4.1 and AQP4 suggests that Müller 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.
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, 00161, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gaddini
authors.affiliation: GB Bietti Eye Foundation IRCCS, Via Livenza, 3, Rome, 00198, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Varano
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, 00161, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Matteucci
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, 00161, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Mallozzi
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, 00161, Italy.
authors.forename: Marika
authors.initials: M
authors.lastname: Villa
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, 00161, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Pricci
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome, 00161, Italy. Electronic address: fiorella.malchiodialbedi@iss.it.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Malchiodi-Albedi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004586:Electrophoresis; D063928:Ependymoglial Cells / Q000378:metabolism* / Q000473:pathology; D005136:Eye Proteins / Q000378:metabolism*; D008268:Macular Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D000069579:Ranibizumab / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D040262:Receptors, Vascular Endothelial Growth Factor; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D005136:Eye Proteins; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab
keywords: Aflibercept; Aquaporin 4; Glial Fibrillary Acidic Protein; K(+) channel 4.1; Müller glia; Primary retinal cultures; Ranibizumab; Vascular Endothelial Growth Factor