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Trends Mol Med. 2010 Sep;16(9):417-25. doi: 10.1016/j.molmed.2010.07.003. Epub 2010 Aug 3.

The Norrin/Frizzled4 signaling pathway in retinal vascular development and disease.

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  • 1Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Disorders of retinal vascular growth and function are responsible for vision loss in a variety of diseases, including diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity and retinal artery or vein occlusion. Over the past decade, a new signaling pathway that controls retinal vascular development has emerged from the study of inherited disorders - in both humans and mice - that are characterized by retinal hypovascularization. This pathway utilizes a glial-derived extracellular ligand, Norrin, that acts on a transmembrane receptor, Frizzled4, a coreceptor, Lrp5, and an auxiliary membrane protein, Tspan12, on the surface of developing endothelial cells. The resulting signal controls a transcriptional program that regulates endothelial growth and maturation. It will be of great interest to determine whether modulating this pathway could represent a therapeutic approach to human retinal vascular disease.

Copyright 2010 Elsevier Ltd. All rights reserved.

PMID:
20688566
[PubMed - indexed for MEDLINE]
PMCID:
PMC2963063
Free PMC Article
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