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Graefe's Archive for Clinical and Experimental Ophthalmology

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Open Access 01-10-2013 | Basic Science

Ranibizumab efficiently blocks migration but not proliferation induced by growth factor combinations including VEGF in retinal endothelial cells

Authors: Heidrun L. Deissler, Helmut Deissler, Gerhard K. Lang, Gabriele E. Lang

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 10/2013

Abstract

Background

Proliferation and migration of retinal endothelial cells (REC) are associated with the development of proliferative diabetic retinopathy. REC proliferation is stimulated by isoforms of vascular endothelial growth factor-A (i.e., VEGF₁₂₁ and VEGF₁₆₅), basic fibroblast growth factor (bFGF), and insulin-like growth factor (IGF-1) of which VEGF₁₆₅ also enhances migration of REC. Effects induced by VEGF-A can be blocked with ranibizumab, a VEGF-binding Fab fragment used in therapy of diabetic macular edema. In this study, we investigated potential angiogenic effects of placental growth factors (PlGF-1, PlGF-2) as other members of the VEGF family and whether the primary action of VEGF₁₆₅ is modulated in the presence of bFGF, IGF-1 and PlGF-1/-2. We also studied how effects of growth factor combinations can be attenuated with ranibizumab.

Methods

Effects of single growth factors or their combinations on proliferation and migration of immortalized bovine retinal endothelial cells (iBREC) were studied with or without ranibizumab or the inhibitor of VEGF receptors KRN951.

Results

Proliferation of iBREC was significantly stimulated by 1–100 ng/ml PlGF-1 or PlGF-2, but additive effects were not observed with various combinations of the tested growth factors. Ranibizumab neutralized VEGF’s effect on proliferation but was not effective when the other growth factors were used in combination with VEGF. bFGF and IGF-1 but not PlGF-1 or PlGF-2 stimulated iBREC migration as single agents, and they further enhanced VEGF-induced migration. The effects of such growth factor combinations including VEGF on migration were efficiently blocked by targeting only VEGF with ranibizumab. Migration induced by VEGF plus bFGF and IGF-1 was also almost completely inhibited by KRN951 interfering with VEGF receptor signalling.

Conclusions

Migration but not proliferation of iBREC induced by combinations of bFGF, IGF-1, PlGF-1 or PlGF-2 together with VEGF is efficiently suppressed by ranibizumab. VEGF-mediated signalling through VEGFR2 seems to control REC migration dominantly in the presence of other growth factors.

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Title: Ranibizumab efficiently blocks migration but not proliferation induced by growth factor combinations including VEGF in retinal endothelial cells
Authors: Heidrun L. Deissler
Helmut Deissler
Gerhard K. Lang
Gabriele E. Lang
Publication date: 01-10-2013
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 10/2013
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-013-2393-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Ranibizumab efficiently blocks migration but not proliferation induced by growth factor combinations including VEGF in retinal endothelial cells

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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