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E. A. Stewart, W. M. K. Amoaku; The in vitro Effects of Anti-Angiogenic Treatments on Human Choroidal Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2354.
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Age-related macular degeneration (AMD) is the most common cause of irreversible visual loss in elderly populations in the western world. Neovascularisation by choroidal endothelial cells (hCEC) causes AMD; however, the mechanisms responsible are not fully understood. Vascular endothelial growth factor (VEGF) is thought to be the most significant growth factor in AMD and subsequently, molecular inhibitors including pegaptanib (Macugen), ranibizumab (Lucentis) and bevacizumab (Avastin) have been developed as treatments for AMD.
hCEC were isolated from cadaver eyes and cultured in EBM2-MV medium as previously published. hCEC proliferation after exposure to VEGF isoforms 165 and 121 and anti-angiogenic treatments was measured using the WST-1 assay. The effect of the VEGF isoforms and anti-angiogenic treatments on angiogenesis was assessed using a double layer Matrigel technique.
hCEC proliferation in response to VEGF 121 and 165 was found to be equivalent. Individually and in combination both Ranibizumab (Lucentis) and bevacizumab (Avastin) were effective in decreasing proliferation of hCEC. Pegaptanib (Macugen) was moderately effective in controlling the proliferation of hCEC stimulated by VEGF 165, but was ineffective against the stimulatory effect of VEGF 121.
Although molecular inhibitors of angiogenesis have been shown to have a beneficial effect as treatments for AMD, direct comparison of the efficiency of the drugs is complicated, due to variations between trials and dosing regimes. In vitro testing of the drugs on the proliferation and angiogenesis of hCEC showed that the efficacy is in the order Lucentis>Avastin>Macugen, in line with the current clinical outcomes seen.
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