| Different properties of VEGF-antagonists: Bevacizumab but not Ranibizumab accumulates in RPE cells. | |
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MedLine Citation:
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PMID: 19597740 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Vascular endothelial growth factor (VEGF) antagonists are currently the therapy of choice for age-related macular degeneration. Here we compared the effects of FDA-approved Ranibizumab and off-label used Bevacizumab on RPE cells, investigating their respective uptake by RPE cells over time. METHODS: Primary porcine RPE cells were treated with Bevacizumab or Ranibizumab, respectively. Uptake of the respective VEGF-antagonists was assessed with confocal laser scanning microscopy and flow cytometry. Cell death was assessed with MTT assay and VEGF secretion was measured with ELISA. RESULTS: When clinical doses were applied for 1 h, Bevacizumab was taken up by RPE cells as assessed by confocal laser scanning microscopy and flow cytometry. After 24 h of incubation, and further assessed after 1d, 5d, and 7d, Bevacizumab was detected in RPE cells where it accumulated over time. The presence of Bevacizumab within RPE cells after 7d was confirmed by flow cytometry. While some Ranibizumab was found in RPE cells after 1 h of incubation when assessed with confocal laser microscopy but not by flow cytometry, no signal above control was detected after 1d, 5d, or 7d. Neither substance induced significant cell death after 7 days and no inhibitory effect on VEGF secretion was observed after day 3 of culture. CONCLUSIONS: Bevacizumab, but not Ranibizumab, accumulates in RPE cells over time, implying substantial differences between these two drugs. |
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Authors:
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Alexa Karina Klettner; Marie-Luise Kruse; Tim Meyer; Daniela Wesch; Dieter Kabelitz; Johann Roider |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-07-14 |
Journal Detail:
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Title: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie Volume: 247 ISSN: 1435-702X ISO Abbreviation: Graefes Arch. Clin. Exp. Ophthalmol. Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-11-12 Completed Date: 2009-12-11 Revised Date: 2013-05-27 |
Medline Journal Info:
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Nlm Unique ID: 8205248 Medline TA: Graefes Arch Clin Exp Ophthalmol Country: Germany |
Other Details:
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Languages: eng Pagination: 1601-8 Citation Subset: IM |
Affiliation:
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Department of Ophthalmology, University of Kiel, Campus Kiel, Hegewischstr. 2, 24105 Kiel, Germany. aklettner@ophthalmol.uni-kiel.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenesis Inhibitors
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pharmacology* Animals Antibodies, Monoclonal / pharmacology* Antibodies, Monoclonal, Humanized Cell Survival Cells, Cultured Enzyme-Linked Immunosorbent Assay Flow Cytometry Microscopy, Confocal Organ Culture Techniques Retinal Pigment Epithelium / drug effects*, metabolism Swine Vascular Endothelial Growth Factor A / antagonists & inhibitors*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Angiogenesis Inhibitors; 0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Vascular Endothelial Growth Factor A; 0/ranibizumab; 2S9ZZM9Q9V/bevacizumab |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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