April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Mitochondrial Membrane Potential Response of Retinal Pigment Epithelium Cells In Vitro to Anti-VEGF Agents: Ranibizumab, Bevacizumab, Aflibercept and Ziv-aflibercept
Author Affiliations & Notes
  • Deepika Malik
    Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA
  • Javier Caceres del Carpio
    Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA
  • Young Gyun Kim
    Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA
    Eulji University, Seoul, Republic of Korea
  • Mohamed Tarek Mohamed Moustafa
    Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA
  • Kunal Thaker
    Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA
  • Tej Patel
    Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA
  • Simon R Bababeygy
    Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA
  • Cristina M Kenney
    Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA
  • Baruch Kuppermann
    Ophthalmology, Gavin Herbert Eye Institute, University of California, Irvine, CA
  • Footnotes
    Commercial Relationships Deepika Malik, None; Javier Caceres del Carpio, None; Young Gyun Kim, None; Mohamed Tarek Mohamed Moustafa, None; Kunal Thaker, None; Tej Patel, None; Simon Bababeygy, None; Cristina Kenney, None; Baruch Kuppermann, Alcon (C), Alimera (C), Allegro (C), Allergan (C), Genentech (C), Glaukos (C), GSK (C), Neurotech (C), Novagali (C), Novartis (C), Ophthotech (C), Pfizer (C), Regeneron (C), Santen (C), SecondSight (C), Teva (C), Thrombogenics (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 599. doi:
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      Deepika Malik, Javier Caceres del Carpio, Young Gyun Kim, Mohamed Tarek Mohamed Moustafa, Kunal Thaker, Tej Patel, Simon R Bababeygy, Cristina M Kenney, Baruch Kuppermann; Mitochondrial Membrane Potential Response of Retinal Pigment Epithelium Cells In Vitro to Anti-VEGF Agents: Ranibizumab, Bevacizumab, Aflibercept and Ziv-aflibercept. Invest. Ophthalmol. Vis. Sci. 2014;55(13):599.

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

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Abstract
 
Purpose
 

Vascular endothelial growth factor (VEGF) plays an important role in normal retinal function and in maintenance of the choriocapillaris by the retinal pigment epithelium (RPE). Chronic use of anti-VEGF agents to treat wet age-related macular degeneration (AMD), while of obvious net benefit to patients, may also lead to progression of geographic atrophy and dry AMD in treated eyes. Experimental studies have shown the presence of VEGF-blockade toxicity in retinal ganglion cells, photoreceptors and choriocapillaris in mouse models. The aim of this study was to compare the effects of anti-VEGF drugs on mitochondrial membrane potential of RPE cells in culture in order to determine if these drugs have measurable and differing safety profiles.

 
Methods
 

Human RPE cells (ARPE-19) were exposed for 24 hours to one of the four anti-VEGF drugs at 1/2X, 1X, 2X or 10X clinical concentrations (X= drug dose per 4 ml of culture media: ranibizumab, 0.5mg; bevacizumab, 1.25mg; aflibercept, 2mg; ziv-aflibercept, 2mg). Mitochondrial membrane potential assay using JC-1 dye was performed to evaluate early apoptotic changes as a marker of cell damage rather than frank cell death.

 
Results
 

Mitochondrial membrane potential was not significantly decreased at one half the clinical dose (1/2X) for any of the four drugs tested. Similarly, for ranibizumab and aflibercept, cells exposed to 1X clinical dose revealed no significant change in mitochondrial potential. However, bevacizumab and ziv-aflibercept at the 1X clinical dose showed a significant reduction in mitochondrial membrane potential. At supranormal doses, only ranabizumab at the 2X clinical dose did not show a reduction in mitochondrial membrane potential. At 10X clinical dose all four drugs showed significant reductions in mitochondrial membrane potential. (Figure.1)

 
Conclusions
 

At clinical dose (1X), neither ranibizumab nor aflibercept produced evidence of mitochondrial toxicity. However, both bevacizumab and ziv-aflibercept showed mild mitochondrial toxicity at clinically equivalent doses. At supranormal doses, only ranibizumab at twice the clinical dose showed no significant evidence of mitochondrial toxicity.

 
 
Figure 1. Mitochondrial Membrane Potential of ARPE-19 cells after treatment with Ranibizumab, Bevacizumab, Aflibercept and Ziv-aflibecept. (ns-not significant)
 
Figure 1. Mitochondrial Membrane Potential of ARPE-19 cells after treatment with Ranibizumab, Bevacizumab, Aflibercept and Ziv-aflibecept. (ns-not significant)
 
Keywords: 412 age-related macular degeneration • 701 retinal pigment epithelium • 748 vascular endothelial growth factor  
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