title: Viability of Primary Human Pigment Epithelium Cells and Muller-Glia Cells after Intravitreal Ziv-Aflibercept and Aflibercept.
abstract: OBJECTIVE
  The aim of this study was to access the safety profiles of 2 fusion proteins with anti-vascular endothelial growth factor action (ziv-aflibercept and aflibercept) on retinal pigment epithelium cells and Muller-Glia cells in culture by assessing cell viability post drug exposure.
  
  
  METHODS
  Primary human retinal pigment epithelium cells (pRPE) and Muller-Glia cells (Mio-M1) were exposed to the clinical standardized concentrations of ziv-aflibercept (25 mg/mL) and aflibercept (40 mg/mL). Progressively higher concentrations of NaCl (300, 500, 1,000, 1,500, 2,000, 5,000, and 10,000 mosm/kg) were also applied to cells to assess the possibility of potentiating hyperosmotic cytotoxity effect. The study was applied to measure pRPE and Mio-M1 viability by a tetrazolium dye-reduction assay (XTT).
  
  
  RESULTS
  Cell viability of both pRPE and Mio-M1 presented no significant changes after exposure of ziv-aflibercept and aflibercept. Progressive NaCl concentrations did not significantly alter cell viability. The exposure to the negative control of 75 µL/mL of dimethyl sulfoxide showed significant reduction in cell viability.
  
  
  CONCLUSIONS
  At clinical doses, neither ziv-aflibercept nor aflibercept caused any significant reduction in cell viability in vitro. Furthermore, injection solutions of NaCl with higher osmolality caused no significant reduction in cell viability.
authors.affiliation: Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Costa de Andrade
authors.forename: Christian
authors.initials: C
authors.lastname: Wertheimer
authors.forename: Kirsten
authors.initials: K
authors.lastname: Eibl
authors.forename: Armin
authors.initials: A
authors.lastname: Wolf
authors.forename: Anselm
authors.initials: A
authors.lastname: Kampik
authors.forename: Eduardo
authors.initials: E
authors.lastname: Buchele Rodrigues
authors.forename: Michel Eid
authors.initials: ME
authors.lastname: Farah
authors.forename: Christos
authors.initials: C
authors.lastname: Haritoglou
mesh_terms: D002102:Cadaver; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D063928:Ependymoglial Cells / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D058449:Intravitreal Injections; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000473:pathology*
chemical_list: D011993:Recombinant Fusion Proteins; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor