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Abstract #26369 Published in IGR 12-3
In vitro effects of antivascular endothelial growth factors on cultured human trabecular meshwork cells
Kahook MY; Ammar DAJournal of Glaucoma 2010; 19: 437-441
PURPOSE: To investigate the effects of a neutralizing vascular endothelial growth factor antibody and antibody fragment as well as vehicle components on primary cultures of human trabecular meshwork (TM) cells. METHODS: Assays of cellular metabolism were performed using the diphenyl tetrazolium bromide assay in confluent cultures of cells. Proliferative effects were determined by measuring 5'-bromo-2'-deoxyuridine uptake in subconfluent cultures of cells. RESULTS: Twenty-four-hour treatment with 4 mg/mL bevacizumab reduced TM metabolism to 34.4±12.4% (mean±SD) as compared with human immunoglobulin G controls (P<0.0001). 4 mg/mL bevacizumab also reduced TM cell proliferation to 62.7±9.2% of controls (P<0.0001). No significant decrease was seen at 2 mg/mL bevacizumab, or with molar equivalents of the related anti-vascular endothelial growth factor agent ranibizumab. Exposure of TM cells to the components of bevacizumab and ranibizumab vehicle did not lead to significant antimetabolic effects. CONCLUSIONS: Our data reveal that high concentrations of bevacizumab are harmful to TM cells in vitro whereas no such effect was noted with human immunoglobulin G controls or ranibizumab. Further studies are needed to better understand the antimetabolic effects of higher concentrations of bevacizumab on intraocular cell lines and whether smaller concentrations may have a similar effect on TM cells after repeated exposures.
Department of Ophthalmology, Rocky Mountain Lions Eye Institute, University of Colorado Denver, Aurora, CO.
Classification:
3.6 Cellular biology (Part of: 3 Laboratory methods)
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
