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Role of VEGF‐isoforms in pathological choroidal angiogenesis
Author(s) -
VAN DE VEIRE S,
VAN BERGEN T
Publication year - 2010
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2010.2266.x
Subject(s) - angiogenesis , neovascularization , choroidal neovascularization , gene isoform , cd31 , vascular endothelial growth factor , immunostaining , biology , genetically modified mouse , pathology , transgene , microbiology and biotechnology , medicine , cancer research , ophthalmology , vegf receptors , immunohistochemistry , biochemistry , macular degeneration , gene
Purpose The aim of this project is to study the specific role of the VEGF‐isoforms in pathological angiogenesis, and to investigate the effect of blocking a single isoform on the formation of choroidal neovascularization (CNV). Methods Endothelial and fibroblast cell cultures were made; VEGF 12, 164 or 189 was added to study their effects. VEGF‐isoform specific mice (VEGF 120/+, VEGF 164/164 and VEGF188/188 mice) , as well as double transgenic mice (VEGF 120/164, VEGF 164/188 and VEGF120/188 mice) are used to study the role of VEGF‐isoforms in pathological angiogenesis. At first, these VEGF‐isoform specific mice were backcrossed to a C75Bl/6 background. CNV was induced by placing 3 laser spots at the 9, 12 and 3 o’clock position (100µm spot size, 0.05 s spot duration and 400mW power). Quantification of the area of newly formed blood vessels was determined by retrobulbar dextran linked FITC perfusion. Results Preliminary data in endothelial cell and fibroblast cultures in vitro show that the VEGF121 and VEGF165 isoforms significantly the amount of angiogenesis, whereas the VEGF121 and VEGF189 isoforms play a role in fibrosis. In vivo, the same effects were checked on a fluorescent CD31 and Vimentin immunostaining of the choroids. An inhibition in neovascularization was present in all 3 isoform specific mice, but the effects were comparable. For the moment, mice colonies are being enlarged to repeat experiments and subsequently, these mice are intercrossed to obtain double transgenic mice. Conclusion This study will shed new light on the different role and the inhibition of the VEGF‐isoforms in CNV formation during AMD. Thus, our project may open new perspectives for the treatment of various retinopathies that are known to be associated with VEGF upregulation.