Penetration of bevacizumab and ranibizumab through retinal pigment epithelial layer in vitro

Hiroto Terasaki, Taiji Sakamoto, Makoto Shirasawa, Naoya Yoshihara, Hiroki Otsuka, Shozo Sonoda, Toshio Hisatomi, Tatsuro Ishibashi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Purpose: To determine the permeability of bevacizumab and ranibizumab through highly-polarized retinal pigment epithelial (RPE) cells in vitro. Methods: Highly-polarized RPE cells were cultured in the upper chamber of a Transwell culture system. Bevacizumab or ranibizumab was added to the upper chamber. After 3 hours, the concentrations of bevacizumab or ranibizumab were determined in the upper and lower chambers. The cytotoxicities of the two anti-vascular endothelial growth factor agents were determined histologically. The effects of inhibiting endocytosis by pharmacologic inhibitors were also evaluated. Results: The concentration of ranibizumab was higher than that of bevacizumab in the lower chamber (P < 0.05). Vascular endothelial growth factor was found mainly in the lower chamber under normal conditions. However, the concentration of vascular endothelial growth factor in the lower chamber was significantly less when ranibizumab was added to the upper chamber than when bevacizumab was added. Histology showed no obvious changes in bevacizumab-exposed or ranibizumab-exposed RPE cells. Pretreatment with protein kinase C inhibitor staurosporine had significant negative effects on the permeability of bevacizumab and ranibizumab (P < 0.05). Conclusion: Ranibizumab is more permeable than bevacizumab through the highly-polarized RPE layer at clinically equivalent concentrations, and their permeability was partially protein kinase C-dependent. Ranibizumab might be more therapeutically effective than bevacizumab on choroidal neovascularization beneath the RPE layer.

Original languageEnglish
Pages (from-to)1007-1015
Number of pages9
JournalRetina
Volume35
Issue number5
DOIs
Publication statusPublished - May 8 2015

Fingerprint

Retinal Pigments
Vascular Endothelial Growth Factor A
Permeability
Epithelial Cells
Protein Kinase C
Ranibizumab
Bevacizumab
In Vitro Techniques
Choroidal Neovascularization
Staurosporine
Protein C Inhibitor
Protein Kinase Inhibitors
Endocytosis
Histology

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Terasaki, H., Sakamoto, T., Shirasawa, M., Yoshihara, N., Otsuka, H., Sonoda, S., ... Ishibashi, T. (2015). Penetration of bevacizumab and ranibizumab through retinal pigment epithelial layer in vitro. Retina, 35(5), 1007-1015. https://doi.org/10.1097/IAE.0000000000000428

Penetration of bevacizumab and ranibizumab through retinal pigment epithelial layer in vitro. / Terasaki, Hiroto; Sakamoto, Taiji; Shirasawa, Makoto; Yoshihara, Naoya; Otsuka, Hiroki; Sonoda, Shozo; Hisatomi, Toshio; Ishibashi, Tatsuro.

In: Retina, Vol. 35, No. 5, 08.05.2015, p. 1007-1015.

Research output: Contribution to journalArticle

Terasaki, H, Sakamoto, T, Shirasawa, M, Yoshihara, N, Otsuka, H, Sonoda, S, Hisatomi, T & Ishibashi, T 2015, 'Penetration of bevacizumab and ranibizumab through retinal pigment epithelial layer in vitro', Retina, vol. 35, no. 5, pp. 1007-1015. https://doi.org/10.1097/IAE.0000000000000428
Terasaki H, Sakamoto T, Shirasawa M, Yoshihara N, Otsuka H, Sonoda S et al. Penetration of bevacizumab and ranibizumab through retinal pigment epithelial layer in vitro. Retina. 2015 May 8;35(5):1007-1015. https://doi.org/10.1097/IAE.0000000000000428
Terasaki, Hiroto ; Sakamoto, Taiji ; Shirasawa, Makoto ; Yoshihara, Naoya ; Otsuka, Hiroki ; Sonoda, Shozo ; Hisatomi, Toshio ; Ishibashi, Tatsuro. / Penetration of bevacizumab and ranibizumab through retinal pigment epithelial layer in vitro. In: Retina. 2015 ; Vol. 35, No. 5. pp. 1007-1015.
@article{385bda45c7184122b443a4ec5ede2d7d,
title = "Penetration of bevacizumab and ranibizumab through retinal pigment epithelial layer in vitro",
abstract = "Purpose: To determine the permeability of bevacizumab and ranibizumab through highly-polarized retinal pigment epithelial (RPE) cells in vitro. Methods: Highly-polarized RPE cells were cultured in the upper chamber of a Transwell culture system. Bevacizumab or ranibizumab was added to the upper chamber. After 3 hours, the concentrations of bevacizumab or ranibizumab were determined in the upper and lower chambers. The cytotoxicities of the two anti-vascular endothelial growth factor agents were determined histologically. The effects of inhibiting endocytosis by pharmacologic inhibitors were also evaluated. Results: The concentration of ranibizumab was higher than that of bevacizumab in the lower chamber (P < 0.05). Vascular endothelial growth factor was found mainly in the lower chamber under normal conditions. However, the concentration of vascular endothelial growth factor in the lower chamber was significantly less when ranibizumab was added to the upper chamber than when bevacizumab was added. Histology showed no obvious changes in bevacizumab-exposed or ranibizumab-exposed RPE cells. Pretreatment with protein kinase C inhibitor staurosporine had significant negative effects on the permeability of bevacizumab and ranibizumab (P < 0.05). Conclusion: Ranibizumab is more permeable than bevacizumab through the highly-polarized RPE layer at clinically equivalent concentrations, and their permeability was partially protein kinase C-dependent. Ranibizumab might be more therapeutically effective than bevacizumab on choroidal neovascularization beneath the RPE layer.",
author = "Hiroto Terasaki and Taiji Sakamoto and Makoto Shirasawa and Naoya Yoshihara and Hiroki Otsuka and Shozo Sonoda and Toshio Hisatomi and Tatsuro Ishibashi",
year = "2015",
month = "5",
day = "8",
doi = "10.1097/IAE.0000000000000428",
language = "English",
volume = "35",
pages = "1007--1015",
journal = "Retina",
issn = "0275-004X",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Penetration of bevacizumab and ranibizumab through retinal pigment epithelial layer in vitro

AU - Terasaki, Hiroto

AU - Sakamoto, Taiji

AU - Shirasawa, Makoto

AU - Yoshihara, Naoya

AU - Otsuka, Hiroki

AU - Sonoda, Shozo

AU - Hisatomi, Toshio

AU - Ishibashi, Tatsuro

PY - 2015/5/8

Y1 - 2015/5/8

N2 - Purpose: To determine the permeability of bevacizumab and ranibizumab through highly-polarized retinal pigment epithelial (RPE) cells in vitro. Methods: Highly-polarized RPE cells were cultured in the upper chamber of a Transwell culture system. Bevacizumab or ranibizumab was added to the upper chamber. After 3 hours, the concentrations of bevacizumab or ranibizumab were determined in the upper and lower chambers. The cytotoxicities of the two anti-vascular endothelial growth factor agents were determined histologically. The effects of inhibiting endocytosis by pharmacologic inhibitors were also evaluated. Results: The concentration of ranibizumab was higher than that of bevacizumab in the lower chamber (P < 0.05). Vascular endothelial growth factor was found mainly in the lower chamber under normal conditions. However, the concentration of vascular endothelial growth factor in the lower chamber was significantly less when ranibizumab was added to the upper chamber than when bevacizumab was added. Histology showed no obvious changes in bevacizumab-exposed or ranibizumab-exposed RPE cells. Pretreatment with protein kinase C inhibitor staurosporine had significant negative effects on the permeability of bevacizumab and ranibizumab (P < 0.05). Conclusion: Ranibizumab is more permeable than bevacizumab through the highly-polarized RPE layer at clinically equivalent concentrations, and their permeability was partially protein kinase C-dependent. Ranibizumab might be more therapeutically effective than bevacizumab on choroidal neovascularization beneath the RPE layer.

AB - Purpose: To determine the permeability of bevacizumab and ranibizumab through highly-polarized retinal pigment epithelial (RPE) cells in vitro. Methods: Highly-polarized RPE cells were cultured in the upper chamber of a Transwell culture system. Bevacizumab or ranibizumab was added to the upper chamber. After 3 hours, the concentrations of bevacizumab or ranibizumab were determined in the upper and lower chambers. The cytotoxicities of the two anti-vascular endothelial growth factor agents were determined histologically. The effects of inhibiting endocytosis by pharmacologic inhibitors were also evaluated. Results: The concentration of ranibizumab was higher than that of bevacizumab in the lower chamber (P < 0.05). Vascular endothelial growth factor was found mainly in the lower chamber under normal conditions. However, the concentration of vascular endothelial growth factor in the lower chamber was significantly less when ranibizumab was added to the upper chamber than when bevacizumab was added. Histology showed no obvious changes in bevacizumab-exposed or ranibizumab-exposed RPE cells. Pretreatment with protein kinase C inhibitor staurosporine had significant negative effects on the permeability of bevacizumab and ranibizumab (P < 0.05). Conclusion: Ranibizumab is more permeable than bevacizumab through the highly-polarized RPE layer at clinically equivalent concentrations, and their permeability was partially protein kinase C-dependent. Ranibizumab might be more therapeutically effective than bevacizumab on choroidal neovascularization beneath the RPE layer.

UR - http://www.scopus.com/inward/record.url?scp=84929044499&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929044499&partnerID=8YFLogxK

U2 - 10.1097/IAE.0000000000000428

DO - 10.1097/IAE.0000000000000428

M3 - Article

C2 - 25627091

AN - SCOPUS:84929044499

VL - 35

SP - 1007

EP - 1015

JO - Retina

JF - Retina

SN - 0275-004X

IS - 5

ER -