University of Oulu

Elamaa, H., Kihlström, M., Kapiainen, E., Kaakinen, M., Miinalainen, I., Ragauskas, S., Cerrada-Gimenez, M., Mering, S., Nätynki, M. & Eklund, L. (2018) Angiopoietin-4-dependent venous maturation and fluid drainage in the peripheral retina. eLife, 7, e37776. doi:10.7554/eLife.37776.001

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

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Author: Elamaa, Harri1,2; Kihlström, Minna1,2; Kapiainen, Emmi1,2;
Organizations: 1Oulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, University of Oulu
2Biocenter Oulu, University of Oulu
3R&D Department, Experimentica Ltd
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 21.6 MB)
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Language: English
Published: eLife Sciences Publications, 2018
Publish Date: 2019-01-03


The maintenance of fluid homeostasis is necessary for function of the neural retina; however, little is known about the significance of potential fluid 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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Series: eLife
ISSN: 2050-084X
ISSN-E: 2050-084X
ISSN-L: 2050-084X
Volume: 7
Article number: e37776
DOI: 10.7554/eLife.37776.001
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This research was supported by the Academy of Finland grants to LE (251314, 136880, 310986).
Academy of Finland Grant Number: 251314
Detailed Information: 251314 (Academy of Finland Funding decision)
136880 (Academy of Finland Funding decision)
310986 (Academy of Finland Funding decision)
Dataset Reference: Supplementary files:
Copyright information: © 2018, Elamaa et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.