Schlecht, Anja and Leimbeck, Sarah V. and Jagle, Herbert and Feuchtinger, Annette and Tamm, Ernst R. and Braunger, Barbara M. (2017) Deletion of Endothelial Transforming Growth Factor-beta Signaling Leads to Choroidal Neovascularization. AMERICAN JOURNAL OF PATHOLOGY, 187 (11). pp. 2570-2589. ISSN 0002-9440, 1525-2191
Full text not available from this repository. (Request a copy)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)-beta signaling for CNV formation by generating a series of mutant mouse models with induced conditional deletion of TGF-beta signaling in the entire eye, the retinal pigment epithelium (RPE), or the vascular endothelium. Deletion of TGF-beta 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-beta 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-beta signaling in the vascular endothelium of the eye is sufficient to trigger CNV formation. Our findings highlight the importance of TGF-beta signaling as a key player in the development of ocular neovascularization and indicate a fundamental role of TGF-beta signaling in the pathogenesis of age-related macular degeneration.
| Item Type: | Article |
|---|---|
| Uncontrolled 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; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie > Prof. Dr. Ernst Tamm |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:19 |
| Last Modified: | 19 Feb 2019 13:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1937 |
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