Effect of VEGF and anti-VEGF compounds on retinal pigment epithelium permeability: an in vitro study

Purpose: To evaluate the effect of 2 vascular endothelial growth factor (VEGF) isoforms (121 and 165) and 2 anti-VEGF compounds (ranibizumab and pegaptanib sodium) on the permeability of human retinal pigment epithelium (RPE) cells in vitro. Methods: The RPE permeability was assessed on ARPE19 cells grown onto inserts of polytetrafluoroethylene previously treated with ammonia gas plasma. Paracellular permeability to ions was measured by mean of transepithelial electrical resistance (TEER). Permeability to non-ionic molecules was gathered by the amount of fluorescein dextran (FD) passing across the monolayer within 2 hours. Results: Only VEGF165 applied at the apical side of the monolayer induced a statistically significant decrease of TEER (p<0.001). No changes in TEER were observed when pegaptanib sodium or ranibizumab were apically administered together with VEGF165. Both VEGF isoforms significantly increased permeability to 4 kDa dextran (p<0.01). Apical administration of ranibizumab or pegaptanib sodium as well as coadministration of pegaptanib sodium with VEGF121 or VEGF165 induced a statistically significant increase of permeability to 4 kDa FD. Conclusions: Both VEGF isoforms and anti-VEGF compounds exert an effect on human RPE permeability in vitro.