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Suk Jin Kim, Kyong Sil Kim, Myung Hun Yoon, Na Rae Kim, Hee Seung Chin; Effects of Bevacizumab on Bcl-2 Expression and Apoptosis in Retinal Pigment Epithelial Cells under Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4284.
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To evaluate the effects of bevacizumab on expression of Bcl-2, Bcl-XL and apoptosis in retinal pigment epithelial (RPE) cells under oxidative stress.
RPE cells were treated with H2O2 (50,100,200,300,400µM) and bevacizumab at or above the dose normally used in clinical practice (0.33, 0.67, 1.33, 2.67mg/ml). Cell death was measured by flow cytometry with annexin V-FITC. The expression of Bcl-2 and Bcl-XL mRNA was determined by RT-PCR.
Under low oxidative stress conditions (50 and 100 µM), cell apoptosis was not significantly different at all concentrations of bevacizumab. Bcl-2 mRNA expression were decreased by increasing concentrations of bevacizumab (0.33, 0.67, 1.33, 2.67mg/ml) under low oxidative stress. Under moderate oxidative stress conditions (200 µM), cell survival was increased. Cell survival and Bcl-2 mRNA expression were decreased by increasing concentrations of bevacizumab (0.33, 0.67, 1.33, 2.67mg/ml) under moderate oxidative stress. Under high oxidative stress (300 µM) conditions, cell survival increased at high concentrations of bevacizumab(1.33, 2.67mg/ml), but it did not correlate to Bcl-2 expression. No statistically significant results in the expression of Bcl-XL were observed under any condition.
Withdrawal of VEGF, as in eyes with age-related macular degeneration, leads to RPE cell apoptosis and influences the expression of anti-apoptotic genes such as Bcl-2. Anti-VEGF therapies like bevacizumab should be administered with caution until a definite conclusion can be drawn regarding its safety.
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