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S. Peters, S. Julien, F. Ziemssen, U. Schraermeyer, Tuebingen Bevacizumab Study Group; Bevacizumab Significantly Reduces VEGF–Related Permeability in Choroidal Endothelial Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5343.
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Angiogenesis and VEGF–induced vascular permeability as seen in choroidal neovascular disease (e.g. ARMD) are a major cause for central vision loss. Bevacizumab, a recombinant humanized monoclonal VEGF–antibody, has recently been approved for first–line anti–angiogenic treatment of metastatic colorectal cancer and might be a useful new drug in patients with choroidal neovascularization.
Porcine CEC were seeded onto fibronectin–coated Transwell inserts (pore size 0.4µm, seeding density 30000 cells/cm2). At confluency, growth medium was replaced by assay medium, containing only 1% FCS and no growth factors.Ater 24 hrs, the monolayer was treated with 20ng/ml or 100 ng/ml of VEGF, control wells did not receive any treatment. Bevacizumab (0.1 mg/ml or 1 mg/ml) was then added, again sparing controls from treatment. Permeability of the monolayer was quantified using a FITC–Dextran (70 kD) permeability assay. Fluorescence in the lower Transwell chamber was measured in a TECAN plate reader.
In CEC treated with 20ng/ml VEGF permeability is more than doubled, compared to untreated monolayers. Increasing the dose up to 100 ng/ml does not further promote permeability. Administration of 0.1 mg/ml bevacizumab abates permeability back to the basal flow, which corresponds to a more than 50% reduction in permeability. Higher concentrations of the drug do not have better effects. Significant effects are observed 1–2 hours after treatment, but are most prominent after 3 hours. Treatment with 1 mg/ml Avastin in the absence of growth factors does not alter the permeability of the CEC–monolayer.
Bevacizumab significantly reduces VEGF–related permeability of choroidal endothelial cells and therefore represents a useful new agent in treatment of choroidal neovascular disease with increased vascular leakage. Permeability is reduced to the amount of an untreated CEC monolayer. Direct application of the drug to the cells does not cause functional damage to the cells in terms of permeability.
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