title: Different Ipsi- and Contralateral Glial Responses to Anti-VEGF and Triamcinolone Intravitreal Injections in Rats.
abstract: OBJECTIVE
  To investigate the glial response of the rat retina to single or repeated intravitreal injections (IVI).
  
  
  METHODS
  Albino Sprague-Dawley rats received one or three (one every 7 days) IVI of anti-rat VEGF (5 μL; 0.015 μg/μL), triamcinolone (2.5 or 5 μL; 40 μg/μL; Trigón Depot), bevacizumab (5 μL; 25 μg/μL; Avastin), or their vehicles (PBS and balanced salt solution) and were processed 7 days after the last injection. Retinas were dissected as whole mounts and incubated with antibodies against: Iba1 (Ionized Calcium-Binding Adapter Molecule 1) to label retinal microglia, GFAP (Glial Fibrillary Acidic Protein) to label macroglial cells, and vimentin to label Müller cells. The retinas were examined with fluorescence and confocal microscopy, and the numbers of microglial cells in the inner retinal layers were quantified using a semiautomatic method.
  
  
  RESULTS
  All the injected substances caused an important micro- and macroglial response locally at the injection site and all throughout the injected retina that was exacerbated by repeated injections. The microglial response was also observed but was milder in the contralateral noninjected eyes. The IVI of the humanized antibody bevacizumab caused a very strong microglial reaction in the ipsilateral retina. Two types of macroglial response were observed: astrocyte hypertrophy and Müller end-foot hypertrophy. While astrocyte hypertrophy was widespread throughout the injected retina, Müller end-foot hypertrophy was localized and more extensive with triamcinolone use or after repeated injections.
  
  
  CONCLUSIONS
  Intravitreal injections cause micro- and macroglial responses that vary depending on the injected agent but increase with repeated injections. This inflammatory glial response may influence the effects of the injected substances on the retina.
authors.forename: Johnny
authors.initials: J
authors.lastname: Di Pierdomenico
authors.forename: Diego
authors.initials: D
authors.lastname: García-Ayuso
authors.forename: Manuel
authors.initials: M
authors.lastname: Jiménez-López
authors.forename: Marta
authors.initials: M
authors.lastname: Agudo-Barriuso
authors.forename: Manuel
authors.initials: M
authors.lastname: Vidal-Sanz
authors.forename: María Paz
authors.initials: MP
authors.lastname: Villegas-Pérez
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D000068258:Bevacizumab / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000494:pharmacology; D058449:Intravitreal Injections; D008840:Microfilament Proteins / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects*; D014221:Triamcinolone / Q000008:administration & dosage / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D014746:Vimentin / Q000494:pharmacology
chemical_list: C100745:Aif1 protein, rat; D020533:Angiogenesis Inhibitors; D000906:Antibodies; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D042461:Vascular Endothelial Growth Factor A; D014746:Vimentin; D014221:Triamcinolone; D000068258:Bevacizumab