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Publication : Angiopoietin-4-dependent venous maturation and fluid drainage in the peripheral retina.

First Author  Elamaa H Year  2018
Journal  Elife Volume  7
PubMed ID  30444491 Mgi Jnum  J:267502
Mgi Id  MGI:6266979 Doi  10.7554/eLife.37776
Citation  Elamaa H, et al. (2018) Angiopoietin-4-dependent venous maturation and fluid drainage in the peripheral retina. Elife 7:e37776
abstractText  The maintenance of fluid homeostasis is necessary for function of the neural retina; however, little is known about the significance of potential fl uid management mechanisms. Here, we investigated angiopoietin-4 (Angpt4, also known as Ang3), a poorly characterized ligand for endothelial receptor tyrosine kinase Tie2, in mouse retina model. By using genetic reporter, fate mapping, and in situ hybridization, we found Angpt4 expression in a specific sub-population of astrocytes at the site where venous morphogenesis occurs and that lower oxygen tension, which distinguishes peripheral and venous locations, enhances Angpt4 expression. Correlating with its spatiotemporal expression, deletion of Angpt4 resulted in defective venous development causing impaired venous drainage and defects in neuronal cells. In vitro characterization of angiopoietin-4 proteins revealed both ligand-specific and redundant functions among the angiopoietins. Our study identifies Angpt4 as the first growth factor for venous-specific development and its importance in venous remodeling, retinal fluid clearance and neuronal function.
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