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

作者：Schlecht Anja; Leimbeck Sarah V; Jagle Herbert; Feuchtinger Annette; Tamm Ernst R^*; Braunger Barbara M^*

来源：American Journal Of Pathology, 2017, 187(11): 2570-2589.

DOI：10.1016/j.ajpath.2017.06.018

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.

• 出版日期2017-11