Journal article

Publication year: 2022

Journal: Biomolecules

Volume number: 12

Issue number: 5

eISSN: 2218-273X

Open access status: Gold

DOI Link: https://doi.org/10.3390/biom12050734

Publisher: MDPI

Abstract: 
As responses of immortalized endothelial cells of the bovine retina (iBREC) to VEGF-A(165) depend on exposure time to the growth factor, we investigated changes evident after long-term treatment for nine days. The cell index of iBREC cultivated on gold electrodes-determined as a measure of permeability-was persistently reduced by exposure to the growth factor. Late after addition of VEGF-A(165) protein levels of claudin-1 and CD49e were significantly lower, those of CD29 significantly higher, and the plasmalemma vesicle associated protein was no longer detected. Nuclear levels of beta-catenin were only elevated on day two. Extracellular levels of VEGF-A-measured by ELISA-were very low. Similar to the binding of the growth factor by brolucizumab, inhibition of VEGFR2 by tyrosine kinase inhibitors tivozanib or nintedanib led to complete, although transient, recovery of the low cell index when added early, though was inefficient when added three or six days later. Additional inhibition of other receptor tyrosine kinases by nintedanib was similarly unsuccessful, but additional blocking of c-kit by tivozanib led to sustained recovery of the low cell index, an effect observed only when the inhibitor was added early. From these data, we conclude that several days after the addition of VEGF-A(165) to iBREC, barrier dysfunction is mainly sustained by increased paracellular flow and impaired adhesion. Even more important, these changes are most likely no longer VEGF-A-controlled.

Harvard Citation style: Deissler, H., Rehak, M. and Wolf, A. (2022) Impairment of the Retinal Endothelial Cell Barrier Induced by Long-Term Treatment with VEGF-A₁₆₅ No Longer Depends on the Growth Factor's Presence, Biomolecules, 12(5), Article 734. https://doi.org/10.3390/biom12050734

APA Citation style: Deissler, H., Rehak, M., & Wolf, A. (2022). Impairment of the Retinal Endothelial Cell Barrier Induced by Long-Term Treatment with VEGF-A₁₆₅ No Longer Depends on the Growth Factor's Presence. Biomolecules. 12(5), Article 734. https://doi.org/10.3390/biom12050734