In vitro effects of antivascular endothelial growth factors on cultured human trabecular meshwork cells.
OBJECTIVE
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.
Kahook
Malik Y
MY
Department of Ophthalmology, Rocky Mountain Lions Eye Institute, University of Colorado Denver, Aurora, CO 80045, USA. Malik.kahook@gmail.com
Ammar
David A
DA
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D006801:Humans; D007128:Immunoglobulin Fragments / Q000633:toxicity; D008875:Middle Aged; D000069579:Ranibizumab; D014129:Trabecular Meshwork / Q000187:drug effects* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007128:Immunoglobulin Fragments; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab