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Schlecht, A.* ; Leimbeck, S.V.* ; Jägle, H.* ; Feuchtinger, A. ; Tamm, E.R.* ; Braunger, B.M.*

Deletion of endothelial TGF-β signaling leads to choroidal neovascularization.

Am. J. Pathol. 187, 2570-2589 (2017)
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The molecular pathogenesis of choroidal neovascularization (CNV), an angiogenic process that critically contributes to vision loss in age-related macular degeneration (AMD) is unclear. Here we analyzed the role of transforming growth factor (TGF)-β signaling for CNV formation by generating a series of mutant mouse models with induced conditional deletion of TGF-β signaling in the entire eye, the retinal pigment epithelium (RPE) or the vascular endothelium. Deletion of TGF-β signaling in the eye caused CNV, irrespectively if it was ablated in newborn or three-week-old mice. Areas of CNV showed photoreceptor degeneration, multilayered RPE, basal lamina deposits and accumulations of monocytes/macrophages. The changes progressed leading to marked structural and functional alterations of the retina. While the specific deletion of TGF-β signaling in the RPE caused no obvious changes, specific deletion in vascular endothelial cells caused CNV and a phenotype quite similar to that observed after the deletion in the entire eye. We conclude that impairment of TGF-β signaling in the vascular endothelium of the eye is sufficient to trigger CNV formation. Our findings highlight the importance of TGF-β signaling as key player in the development of ocular neovascularization and indicate a fundamental role of TGF-β signaling in the pathogenesis of AMD.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Retinal-pigment Epithelium; Activated Protein-kinase; Basal Laminar Deposit; Macular Degeneration; Tgf-beta; Immunohistochemical Localization; Fenestrated Endothelia; Tgf-beta-1 Expression; Diabetic-retinopathy; Electron-microscopy
ISSN (print) / ISBN 0002-9440
e-ISSN 1525-2191
Quellenangaben Volume: 187, Issue: 11, Pages: 2570-2589 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place New York
Reviewing status Peer reviewed