PURPOSE: The neovascular or wet form of age-related macular degeneration is characterized by the growth of abnormal blood vessels in the retina stimulated by vascular endothelial growth factors (VEGF). In the last decade, several anti-VEGF drugs have been developed for treating neovascular diseases of the eyes. This study was conducted to compare the effects of 2 anti-VEGF-A drugs, ranibizumab and aflibercept, on the expression and secretion of VEGF family members in retinal pigment epithelial cells (RPE) in vitro. METHODS: ARPE-19 cells were exposed for 24 hours to ranibizumab or aflibercept at clinical dose concentration. Cell viability and expression and secretion of VEGF-A, VEGF-B, VEGF-C, and placental growth factor (PlGF) were evaluated respectively by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Ranibizumab and aflibercept did not affect ARPE-19 cell viability after 24 hours of treatment. Ranibizumab increased expression of VEGF-A and PlGF. On the contrary, expression and secretion of VEGF-C was decreased by ranibizumab. PlGF secretion was not affected by ranibizumab. Aflibercept strongly increased VEGF-A and PlGF expression but reduced their detection on the culture media, and decreased expression and secretion of VEGF-C. No effect on expression and secretion of VEGF-B was observed after exposure to these drugs. CONCLUSIONS: Ranibizumab and aflibercept exert similar effects on VEGF expression and secretion, leading to establishing an antiangiogenic environment. Increased VEGF-A expression observed in RPE cells treated with these drugs suggests a compensatory response of the cells to the lack of VEGF-A.

Response to anti-VEGF-A treatment of retinal pigment epithelial cells in vitro.

PUDDU, ALESSANDRA;SANGUINETI, ROBERTA;TRAVERSO, CARLO;VIVIANI, GIORGIO LUCIANO;NICOLO', MASSIMO
2016-01-01

Abstract

PURPOSE: The neovascular or wet form of age-related macular degeneration is characterized by the growth of abnormal blood vessels in the retina stimulated by vascular endothelial growth factors (VEGF). In the last decade, several anti-VEGF drugs have been developed for treating neovascular diseases of the eyes. This study was conducted to compare the effects of 2 anti-VEGF-A drugs, ranibizumab and aflibercept, on the expression and secretion of VEGF family members in retinal pigment epithelial cells (RPE) in vitro. METHODS: ARPE-19 cells were exposed for 24 hours to ranibizumab or aflibercept at clinical dose concentration. Cell viability and expression and secretion of VEGF-A, VEGF-B, VEGF-C, and placental growth factor (PlGF) were evaluated respectively by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Ranibizumab and aflibercept did not affect ARPE-19 cell viability after 24 hours of treatment. Ranibizumab increased expression of VEGF-A and PlGF. On the contrary, expression and secretion of VEGF-C was decreased by ranibizumab. PlGF secretion was not affected by ranibizumab. Aflibercept strongly increased VEGF-A and PlGF expression but reduced their detection on the culture media, and decreased expression and secretion of VEGF-C. No effect on expression and secretion of VEGF-B was observed after exposure to these drugs. CONCLUSIONS: Ranibizumab and aflibercept exert similar effects on VEGF expression and secretion, leading to establishing an antiangiogenic environment. Increased VEGF-A expression observed in RPE cells treated with these drugs suggests a compensatory response of the cells to the lack of VEGF-A.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/842610
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