| First Author | Schlecht A | Year | 2017 |
| Journal | Am J Pathol | Volume | 187 |
| Issue | 11 | Pages | 2570-2589 |
| PubMed ID | 28823871 | Mgi Jnum | J:252504 |
| Mgi Id | MGI:6094312 | Doi | 10.1016/j.ajpath.2017.06.018 |
| Citation | Schlecht A, et al. (2017) Deletion of Endothelial Transforming Growth Factor-beta Signaling Leads to Choroidal Neovascularization. Am J Pathol 187(11):2570-2589 |
| abstractText | 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. |
