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Effects of Bevacizumab on Bcl-2 Expression and Apoptosis in Retinal Pigment Epithelial Cells under Oxidative Stress
Korean Journal of Ophthalmology ; : 424-432, 2015.
Article in English | WPRIM | ID: wpr-219865
ABSTRACT

PURPOSE:

To evaluate the effects of bevacizumab on expression of B-cell leukemia/lymphoma (Bcl)-2 and apoptosis in retinal pigment epithelial (RPE) cells under oxidative stress conditions.

METHODS:

RPE cells were treated with H2O2 (0, 100, 200, 300, and 400 microM) and bevacizumab at or above the doses normally used in clinical practice (0, 0.33, 0.67, 1.33, and 2.67 mg/mL). Cell apoptosis was measured using flow cytometry with annexin V-fluorescein isothiocyanate. The expression of Bcl-2 mRNA was determined using reverse transcription polymerase chain reaction.

RESULTS:

Under low oxidative stress conditions (H2O2 100 microM), cell apoptosis was not significantly different at any concentration of bevacizumab, but Bcl-2 mRNA expression decreased with increasing concentration of bevacizumab (0.33, 0.67, 1.33, and 2.67 mg/mL). Under moderate oxidative stress conditions (H2O2 200 microM), Bcl-2 mRNA expression decreased with increasing concentration of bevacizumab (0.33, 0.67, 1.33, and 2.67 mg/mL), but cell apoptosis increased only at 2.67 mg/mL of bevacizumab. Under high oxidative stress (300 microM) conditions, cell apoptosis increased at high concentrations of bevacizumab (1.33 and 2.67 mg/mL), but it did not correlate with Bcl-2 expression.

CONCLUSIONS:

Withdrawal of vascular endothelial growth factor can lead to RPE cell apoptosis and influences the expression of anti-apoptotic genes such as Bcl-2 under oxidative stress conditions. Since oxidative stress levels of each patient are unknown, repeated injections of intravitreal bevacizumab, as in eyes with age-related macular degeneration, might influence RPE cell survival.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: RNA, Messenger / Enzyme-Linked Immunosorbent Assay / Cell Line / Gene Expression Regulation / Apoptosis / Oxidative Stress / Proto-Oncogene Proteins c-bcl-2 / Angiogenesis Inhibitors / Vascular Endothelial Growth Factor A / Retinal Pigment Epithelium Limits: Humans Language: English Journal: Korean Journal of Ophthalmology Year: 2015 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: RNA, Messenger / Enzyme-Linked Immunosorbent Assay / Cell Line / Gene Expression Regulation / Apoptosis / Oxidative Stress / Proto-Oncogene Proteins c-bcl-2 / Angiogenesis Inhibitors / Vascular Endothelial Growth Factor A / Retinal Pigment Epithelium Limits: Humans Language: English Journal: Korean Journal of Ophthalmology Year: 2015 Type: Article