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Am J Pathol. 2017 Nov;187(11):2570-2589. doi: 10.1016/j.ajpath.2017.06.018. Epub 2017 Aug 18.

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

Author information

1
Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
2
Department of Ophthalmology, University Clinic Regensburg, Regensburg, Germany.
3
Research Unit Analytical Pathology, Helmholtz Zentrum Munich, Munich, Germany.
4
Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany. Electronic address: ernst.tamm@ur.de.
5
Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany. Electronic address: barbara.braunger@ur.de.

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.

PMID:
28823871
DOI:
10.1016/j.ajpath.2017.06.018
[Indexed for MEDLINE]
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