3,4 dihydroxyphenyl ethanol reduces secretion of angiogenin in human retinal pigment epithelial cells

摘要

Background Age-related macular degeneration (AMD) is currently the leading cause of blindness in developed countries. Bevacizumab is a widely used anti-VEGF agent that is a commonly applied therapy for neovascular AMD; however, a consequence of bevacizumab therapy may be the activation of compensatory angiogenic signalling. Combination of bevacizumab with 3,4 dihydroxyphenyl ethanol (DPE) may attenuate this compensatory signalling. The goal of the study was to investigate this therapeutic option in a human retinal pigment epithelial cell line (ARPE-19). Methods ARPE-19 cells were incubated under both normoxic and hypoxic conditions. The cells were treated as follows: control, 100 ??M DPE, 0.25 mg/ml bevacizumab, the combination of DPE and bevacizumab. Media was harvested after 24 h for sandwich ELISAbased angiogenesis assays. The secretion of the following 10 pro-angiogenic cytokines was measured: angiogenin, ANG2, EGF, bFGF, HB-EGF, PDGF-BB, Leptin, PIGF, HGF, and VEGF-A. Results Treatment of ARPE-19 cells with bevacizumab significantly increased the secretion of angiogenin. Secretion of angiogenin and VEGF-A were significantly reduced following treatment with DPE under both normoxia and hypoxia. In addition, angiogenin secretion was significantly reduced following treatment with the combination of DPE and bevacizumab compared to bevacizumab alone. Conclusions Compensatory angiogenic signalling may occur in neovascular AMD following treatment with bevacizumab. Here we show that DPE, both alone and in combination with bevacizumab, can reduce the secretion of angiogenin, a cytokine that has been upregulated following treatment with bevacizumab in RPE cells. Therefore, DPE may represent a possible therapeutic agent to be used in combination with bevacizumab for the treatment of neovascular AMD.