Deletion of Endothelial TGF- β Signaling Leads to Choroidal Neovascularization.

Deletion of Endothelial TGF-β Signaling Leads to Choroidal Neovascularization. Am J Pathol. 2017 Aug 17;: Authors: Schlecht A, Leimbeck SV, Jägle H, Feuchtinger A, Tamm ER, Braunger BM Abstract The molecular pathogenesis of choroidal neovascularization (CNV), an angiogenic process that critically contributes to vision loss in age-related macular degeneration (AMD) is unclear. Here 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 three-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. While 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 quite 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 key player in the development of o...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research