title: PERMEABILITY AND ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR EFFECTS OF BEVACIZUMAB, RANIBIZUMAB, AND AFLIBERCEPT IN POLARIZED RETINAL PIGMENT EPITHELIAL LAYER IN VITRO.
abstract: OBJECTIVE
  To determine the effects of bevacizumab, ranibizumab, and aflibercept on the permeability and the effects of anti-vascular endothelial growth factor (VEGF) on highly polarized retinal pigment epithelial cells (RPECs) in vitro.
  
  
  METHODS
  Highly polarized RPECs were cultured in the upper chamber of a Transwell system. Anti-VEGF antibodies were added to the upper chamber, and the concentrations of the drugs in the lower chambers were measured. The permeability rates of the three anti-VEGF drugs through the RPEC layer and the concentration of VEGF in each chamber were determined.
  
  
  RESULTS
  The permeability of aflibercept was significantly lower by about 40% than that of bevacizumab through the RPEC layer (P < 0.05). Ranibizumab was significantly more permeable through the RPECs than bevacizumab (180% of bevacizumab, P < 0.05). Although VEGF was almost absent in the upper chamber after exposure to the 3 antibodies, it was decreased more significantly with aflibercept than with bevacizumab in the lower chamber (2.8% vs. 65.8% of control; P < 0.01). Ranibizumab also decreased the VEGF level compared with bevacizumab (31.7% vs. 65.8% of control; P < 0.01).
  
  
  CONCLUSIONS
  The greater reduction of the amount of VEGF in the lower chamber by aflibercept and ranibizumab than bevacizumab may explain why aflibercept and ranibizumab are more effective than bevacizumab against type 1 choroidal neovascularization.
authors.affiliation: *Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan;†Department of Laboratory and Vascular Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; and‡Department of Ophthalmology, Kyushu University, Fukuoka, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yoshihara
authors.forename: Hiroto
authors.initials: H
authors.lastname: Terasaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Shirasawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawano
authors.forename: Shozo
authors.initials: S
authors.lastname: Sonoda
authors.forename: Munekazu
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Teruto
authors.initials: T
authors.lastname: Hashiguchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Hisatomi
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Taiji
authors.initials: T
authors.lastname: Sakamoto
mesh_terms: D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000494:pharmacology; D000068258:Bevacizumab / Q000378:metabolism / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000188:drug therapy; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D010539:Permeability / Q000187:drug effects; D000069579:Ranibizumab / Q000378:metabolism / Q000494:pharmacology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism; D012168:Retinal Pigments / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; D012168:Retinal Pigments; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab