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



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.


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.


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.


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.

Eur J Ophthalmol 2016; 26(5): 425 - 430




Alessandra Puddu, Roberta Sanguineti, Carlo Enrico Traverso, Giorgio L. Viviani, Massimo Nicolò

Article History


Financial support: This research was supported by an unconditional research grant from Novartis Farma SpA, which did not influence the planning, conduct, or analysis of the research, writing of the manuscript, or its submission for publication.
Conflict of interest: None of the authors has conflict of interest with this submission.

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  •  Department of Internal Medicine and Medical Specialties, Genova - Italy
  •  Department of Neuroscience, Ophthalmology and Genetics, Genova - Italy
  •  Fondazione per la Macula onlus, Genova - Italy

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