VEGF-induced effects on proliferation, migration and tight junctions are restored by ranibizumab (Lucentis®) in microvascular retinal endothelial cells
- Heidrun L Deissler (heidrun.deissler{at}uni-ulm.de),
- Helmut Deissler (helmut.deissler{at}uniklinik-ulm.de),
- Stefan Lang,
- Gabriele E Lang (gabriele.lang{at}uniklinik-ulm.de)
- University of Ulm Medical School, Germany
- University of Ulm Medical School, Germany
- University of Ulm Medical School, Germany
- University of Ulm Medical School, Germany
- Published Online First 29 May 2008
Abstract
Background/Aims: Because VEGF signalling is deregulated in diabetic retinopathy, potential therapeutic effects of VEGF-inhibitors like the humanised VEGF-specific antibody ranibizumab are currently tested. We therefore investigated if VEGF-stimulated processes in retinal endothelial cells were reverted by ranibizumab.
Methods: The influence of VEGF121 and VEGF165 on proliferation and migration of immortalised bovine retinal endothelial cells (iBREC) were 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: Whereas both isoforms stimulated proliferation of iBREC, only VEGF165 influenced cell migration. Addition of ranibizumab counteracted this stimulation without inhibition of the basal levels of migration and proliferation. Plasma membrane staining of tight junction proteins occludin and claudin-1 disappeared in the presence of VEGF165 by which claudin-5 was not and ZO-1 only weakly affected. Addition of ranibizumab restored plasma membrane localisation of occludin and claudin-1. Only for claudin-1, variation of total protein expression corresponded with observed effects of VEGF165 and ranibizumab.
Conclusion: Ranibizumab reverted proliferation and cell migration stimulated by VEGF and delocalisation of tight junction proteins induced by VEGF165 in iBREC.
