[In vitro studies on the mechanism of action of VEGF and its inhibitors].
VEGF expression and signalling are deregulated in diabetic retinopathy. Cellular processes like migration and proliferation as well as control of the permeability of the endothelium by VEGF are regulated as a consequence of its binding to the VEGF receptor 2. Proteins forming tight junctions between microvascular endothelial cells of the retina are delocated to the cytoplasm after treatment with VEGF(165), likely leading to the breakdown of the blood-retina barrier. VEGF-inhibitors such as a VEGF-aptamer (modified RNA-oligonucleotide; pegaptanib) or specific antibodies/antibody fragments (bevacizumab, ranibzumab) which directly interfere with the interaction of VEGF with its receptors are considered to be promising novel therapeutics to treat diabetic retinopathy and age-related macular degeneration. In vitro studies using microvascular endothelial cells will help to clarify the mechanisms of action of VEGF and its inhibitors. In particular, the influence of VEGF isoforms and the inhibitor ranibizumab on the proliferation and migration of bovine retinal microvascular endothelial cells was studied, as well as the rearrangement of tight-junction proteins after treatment of the cells with VEGF(165) and specific inhibitors. In addition to a review of recent publications in the field, primary data from our own studies are presented in this article.
Deissler
H L
HL
Augenklinik, Universitätsklinikum Ulm. heidrun.deissler@uniklinik-ulm.de
Lang
G E
GE
D000818:Animals; D003930:Diabetic Retinopathy / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor