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Q. Zeng, S. Schaal, H. J. Kaplan, T. H. Tezel; Ability to Bind Fc-Receptors on Retinal Pigment Epithelium (RPE) Can Explain the Higher Occurance of RPE Tears With Bevacizumab (Avastin®) Compared With Ranibizumab (Lucentis®). Invest. Ophthalmol. Vis. Sci. 2010;51(13):4954.
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To determine the ability of bevacizumab and ranibizumab to bind to RPE-cell membranes and induce cell death.
Primary human RPE (phRPE) and ARPE-19 cells were incubated with bevacizumab (625 µg/ml) and ranibizumab (125 µg/ml) with and without 10% human serum. RPE cell death (PI staining) and complement activation was (iC3b) was determined using FACS analysis. Confocal microscopy and iC3b ELISA was used to confirm the results.
3.8% of the RPE cells died 12 hours after incubation with bevacizumab in normoxia. Hypoxia increased membrane-bound VEGF expression 4.0±0.8 times and resulted in a 3.5 fold increase in RPE cell death (13.2±6.5%) with bevacizumab. 57.1% of dying cells were expressing VEGF on their cell membrane. 0.6% of the dying cells stained positive for iC3b on their cell membrane whereas it was completely absent in control sections. Although ranibizumab weakly binds to cell membranes it can not activate complement and result in significant cell death (<1%).
Bevacizumab can effectively bind to membrane-bound VEGF on the RPE cell membrane, activate the complement cascade and result in cell death; in contrast, ranibizumab can not. This difference can explain the higher incidence of RPE-tears reported with bevacizumab. .
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