Deletion of Endothelial Transforming Growth Factor–β Signaling Leads to Choroidal Neovascularization

Schlecht A, Leimbeck SV, Jagle H, Feuchtinger A, Tamm ER, Braunger BM (2017)

Publication Type: Journal article

Publication year: 2017

Journal

American Journal of Pathology American Society for Investigative Pathology (ASIP)

Book Volume: 187

Pages Range: 2570-2589

Journal Issue: 11

DOI: 10.1016/j.ajpath.2017.06.018

Abstract

The molecular pathogenesis of choroidal neovascularization (CNV), an angiogenic process that critically contributes to vision loss in age-related macular degeneration, is unclear. Herein, 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 3-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. Although 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 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 a key player in the development of ocular neovascularization and indicate a fundamental role of TGF-β signaling in the pathogenesis of age-related macular degeneration.

Involved external institutions

Universität Regensburg DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE)

How to cite

APA:

Schlecht, A., Leimbeck, S.V., Jagle, H., Feuchtinger, A., Tamm, E.R., & Braunger, B.M. (2017). Deletion of Endothelial Transforming Growth Factor–β Signaling Leads to Choroidal Neovascularization. American Journal of Pathology, 187(11), 2570-2589. https://doi.org/10.1016/j.ajpath.2017.06.018

MLA:

Schlecht, Anja, et al. "Deletion of Endothelial Transforming Growth Factor–β Signaling Leads to Choroidal Neovascularization." American Journal of Pathology 187.11 (2017): 2570-2589.

BibTeX: Download