September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Fc receptor inhibition reduces susceptibility to oxidative stress in human RPE cells treated with bevacizumab, but not aflibercept.
Author Affiliations & Notes
  • Mahdy Ranjbar
    Ophthalmology, University of Lübeck, Lübeck, Germany
  • Max Philipp Brinkmann
    Ophthalmology, University of Lübeck, Lübeck, Germany
  • Dorinja Zapf
    Ophthalmology, University of Lübeck, Lübeck, Germany
  • Yoko Miura
    Ophthalmology, University of Lübeck, Lübeck, Germany
  • Martin Rudolf
    Ophthalmology, University of Lübeck, Lübeck, Germany
  • Salvatore Grisanti
    Ophthalmology, University of Lübeck, Lübeck, Germany
  • Footnotes
    Commercial Relationships   Mahdy Ranjbar, None; Max Philipp Brinkmann, None; Dorinja Zapf, None; Yoko Miura, None; Martin Rudolf, None; Salvatore Grisanti, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3357. doi:
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      Mahdy Ranjbar, Max Philipp Brinkmann, Dorinja Zapf, Yoko Miura, Martin Rudolf, Salvatore Grisanti; Fc receptor inhibition reduces susceptibility to oxidative stress in human RPE cells treated with bevacizumab, but not aflibercept.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3357.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Anti-vascular endothelial growth factor (VEGF) drugs like aflibercept and bevacizumab have shown to be most effective in treating neovascular age-related macular degeneration (AMD). VEGF-A is induced by oxidative stress, and functions as a survival factor for various cell types, including retinal pigment epithelial (RPE) cells. Uptake of the aforementioned drugs into the RPE has already been shown, with involvement of the Fc receptor (FcR) being assumed, but not demonstrated yet. Herein, we evaluated the significance of the FcR within this context.

Methods : RPE cells were treated with aflibercept and bevacizumab in presence or absence of H2O2 as oxidative stress stimulus. After 24h cells were evaluated for drug uptake, VEGF-A expression and secretion, levels of intracellular reactive oxygen species (ROS) as well as cell proliferation. Experiments were repeated with cells being pre-incubated with an FcR inhibitor prior to drug application.

Results : As expected, aflibercept and bevacizumab inhibited extracellular levels of VEGF-A and were also taken up into the RPE cells. Furthermore, intracellular levels of VEGF-A were significantly reduced. When oxidative stress was applied, intracellular ROS levels in cells treated with aflibercept and bevacizumab rose, and cell proliferation was reduced. Prior incubation with the FcR inhibitor lessened the uptake of bevacizumab, but not aflibercept into RPE cells, and simultaneously enhanced cell survival under oxidative stress conditions.

Conclusions : Our results indicate that uptake and accumulation of aflibercept and bevacizumab within RPE cells affects the intracellular VEGF-A metabolism negatively leading to a biologically relevant reduced cell survival under oxidative stress. The FcR plays a substantial role in the uptake of bevacizumab, but not aflibercept, which allows an enhanced RPE cell survival through FcR blockage in an environment dominated by oxidative stress, as clinically significant for various inflammatory retinal disorders.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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