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Keyvan Koushan, Raluca Rusovici, K V Chalam; Proliferating Retinal Vascular Endothelial Cells are More Sensitive to Bevacizumab than Choroidal Vascular Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1944.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
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