Permeability and anti-vascular endothelial growth factor effects of bevacizumab, ranibizumab, and aflibercept in polarized retinal pigment epithelial layer in vitro

Naoya Yoshihara, Hiroto Terasaki, Makoto Shirasawa, Hiroki Kawano, Shozo Sonoda, Munekazu Yamaguchi, Teruto Hashiguchi, Toshio Hisatomi, Tatsuro Ishibashi, Taiji Sakamoto

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6 Citations (Scopus)

Abstract

Purpose: 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). Conclusion: 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.

Original languageEnglish
Pages (from-to)179-190
Number of pages12
JournalRetina
Volume37
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

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Retinal Pigments
Vascular Endothelial Growth Factor A
Permeability
Epithelial Cells
Choroidal Neovascularization
Ranibizumab
Bevacizumab
aflibercept
In Vitro Techniques
Antibodies
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Ophthalmology

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Permeability and anti-vascular endothelial growth factor effects of bevacizumab, ranibizumab, and aflibercept in polarized retinal pigment epithelial layer in vitro. / Yoshihara, Naoya; Terasaki, Hiroto; Shirasawa, Makoto; Kawano, Hiroki; Sonoda, Shozo; Yamaguchi, Munekazu; Hashiguchi, Teruto; Hisatomi, Toshio; Ishibashi, Tatsuro; Sakamoto, Taiji.

In: Retina, Vol. 37, No. 1, 01.01.2017, p. 179-190.

Research output: Contribution to journalArticle

Yoshihara, N, Terasaki, H, Shirasawa, M, Kawano, H, Sonoda, S, Yamaguchi, M, Hashiguchi, T, Hisatomi, T, Ishibashi, T & Sakamoto, T 2017, 'Permeability and anti-vascular endothelial growth factor effects of bevacizumab, ranibizumab, and aflibercept in polarized retinal pigment epithelial layer in vitro', Retina, vol. 37, no. 1, pp. 179-190. https://doi.org/10.1097/IAE.0000000000001117
Yoshihara, Naoya ; Terasaki, Hiroto ; Shirasawa, Makoto ; Kawano, Hiroki ; Sonoda, Shozo ; Yamaguchi, Munekazu ; Hashiguchi, Teruto ; Hisatomi, Toshio ; Ishibashi, Tatsuro ; Sakamoto, Taiji. / Permeability and anti-vascular endothelial growth factor effects of bevacizumab, ranibizumab, and aflibercept in polarized retinal pigment epithelial layer in vitro. In: Retina. 2017 ; Vol. 37, No. 1. pp. 179-190.
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AU - Yoshihara, Naoya

AU - Terasaki, Hiroto

AU - Shirasawa, Makoto

AU - Kawano, Hiroki

AU - Sonoda, Shozo

AU - Yamaguchi, Munekazu

AU - Hashiguchi, Teruto

AU - Hisatomi, Toshio

AU - Ishibashi, Tatsuro

AU - Sakamoto, Taiji

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Y1 - 2017/1/1

N2 - Purpose: 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). Conclusion: 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.

AB - Purpose: 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). Conclusion: 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.

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