Malik Y Kahook1, David A Ammar. 1. Department of Ophthalmology, Rocky Mountain Lions Eye Institute, University of Colorado Denver, Aurora, CO 80045, USA. Malik.kahook@gmail.com
Abstract
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.
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.
Authors: Joshua A Wood; Clayton T McKee; Sara M Thomasy; Marion E Fischer; Nihar M Shah; Christopher J Murphy; Paul Russell Journal: Invest Ophthalmol Vis Sci Date: 2011-12-02 Impact factor: 4.799
Authors: Lu Liu; David A Ammar; Lindsey A Ross; Naresh Mandava; Malik Y Kahook; John F Carpenter Journal: Invest Ophthalmol Vis Sci Date: 2011-02-22 Impact factor: 4.799