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VEGF-induced effects on proliferation, migration and tight junctions are restored by ranibizumab (Lucentis) in microvascular retinal endothelial cells

2008; BMJ; Volume: 92; Issue: 6 Linguagem: Inglês

10.1136/bjo.2007.135640

1468-2079

Heidrun L. Deissler, Heidrun L. Deissler, Stefan J. Lang, Gabriele E. Lang,

Retinal Imaging and Analysis

Background: Because vascular endothelial growth factor (VEGF) signalling is deregulated in diabetic retinopathy, the potential therapeutic effects of VEGF inhibitors such as the human VEGF-specific antibody ranibizumab are currently being tested. A study was undertaken to determine whether VEGF-stimulated processes in retinal endothelial cells are reversed by ranibizumab. Methods: The influence of VEGF 121 and VEGF 165 on the proliferation and migration of immortalised bovine retinal endothelial cells (iBREC) was studied in the presence and absence of ranibizumab. In addition, the protein composition of tight junctions in the presence of VEGF and its inhibitor in iBREC was investigated. Results: While both isoforms stimulated proliferation of iBREC, only VEGF 165 influenced cell migration. The addition of ranibizumab counteracted this stimulation without inhibition of the basal levels of migration and proliferation. Plasma membrane staining of the tight junction proteins occludin and claudin-1 disappeared in the presence of VEGF 165 ; there was no effect on claudin-5 and ZO-1 was only weakly affected. The addition of ranibizumab restored plasma membrane localisation of occludin and claudin-1. For claudin-1, the variation in total protein expression corresponded with the observed effects of VEGF 165 and ranibizumab. Conclusion: Ranibizumab reverses proliferation and cell migration stimulated by VEGF and delocalisation of tight junction proteins induced by VEGF 165 in iBREC.