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Volker Enzmann, Lorenzo Parisi, Sebastian Wolf; Anti-proliferative properties of aflibercept on retinal cells in vitro. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6536.
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© ARVO (1962-2015); The Authors (2016-present)
Secretion of vascular endothelial growth factor (VEGF) is the cause of choroidal neovascularization (CNV), the hallmark of wet age-related macular degeneration (AMD). Intravitreal application of aflibercept suppresses the unwanted vascularization and improves visual function. Herein, we aim to investigate a direct effect of the anti-VEGF substance on different retinal cell types in vitro.
Concentration-dependent cellular effects of aflibercept (125, 250 μg/ml) were examined using the human Müller cell line MIO-M1, the murine photoreceptor-derived cell line 661W, cultured primary human retinal pigment epithelial cells (hRPE) and murine embryonic fibroblasts (MEF) serving as controls. Cell viability was quantified using the trypan blue exclusion test (400’000 cells/well) after 24 h and 48 h incubation. Cellular growth was detected serial dilution from 5000 to 300 cells/well by XTT-based colorimetric measurement four days after treatment. The anti-VEGF properties of the used substances were assessed by mouse and human-specific ELISAs.
Aflibercept did not decrease cell survival of the tested cell types at the investigated concentrations and time points. However, the treatment decreased cell proliferation of retinal cells but not in the fibroblast controls in a dose-dependent manner. Thereby, the proliferation of MIO-M1 cells was not inhibited by aflibercept 125 μg/ml, whereas 250 μg/ml of the substance reduced the cell growth by 34% (p≦0.01). A similar effect was seen in 661W cultures where the proliferation was significantly reduced by 29% (250 μg/ml, p≦0.01). The proliferation of hRPE was diminished with both aflibercept concentrations by 12% (125 μg/ml, p≤0.0001) or 30% (250 μg/ml, p≤0.0001). VEGF secretion was significantly inhibited in all trials by ≥ 97% compared to the untreated controls.
The anti-VEGF active substance aflibercept is not toxic for retinal glia, photoreceptors and RPE cells in clinically relevant concentrations. However, it shows a retina-specific anti-proliferative effect.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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