Purpose
To evaluate the effect of varying doses of bevacizumab on cell proliferation of vascular endothelial growth factor (VEGF)-enhanced choroidal vascular endothelial and retinal vascular endothelial cells. Even though bevacizumab has been used off-label for treatment of choroidal and retinal vascular diseases, the differential effect of this agent on choroidal and retinal endothelial cell proliferation has not been established.
Methods
Monkey choroidal endothelial RF/6A and human retinal endothelial cells were treated with escalating doses of both VEGF (0-400 ng/ml) and bevacizumab (0.1 to 2.0 mg/ml) for 48h, 72h and 1 week. Cell proliferation changes in response to bevacizumab were analyzed by the WST-1 and trypan blue exclusion assays. Morphological changes were recorded by bright field microscopy of cells.
Results
Cell proliferation analysis of VEGF-enriched CECs and RECs revealed that both cell lines respond to escalating doses of VEGF. Addition of escalating doses of bevacizumab (0.1 to 2.0 mg/ml) decreased CECs proliferation from 10.3% to 17.3% at 48 hours, from 2.35% to 23.7% at 72 hours, and from 4.1% to 17.7% at 1 week. RECs showed a more pronounced suppression of their proliferation in response to bevacizumab, especially at 72-hour and 1-week time points: Addition of escalating doses of bevacizumab (0.1 to 2.0 mg/ml) decreased RECs proliferation from 8.0 % to 23.9% at 48 hours, from -1.58 (non-significant increase) to 46.0% at 72 hours, and from 29.7% to 45.6% at 1 week.
Conclusions
Bevacizumab decreases proliferation of VEGF-enriched choroidal and retinal endothelial cells. This effect is especially pronounced on RECs and should be considered in dosage selection of this drug for treating retinal versus choroidal vascular diseases.
Keywords: 748 vascular endothelial growth factor •
654 proliferation •
700 retinal neovascularization