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

X Ye, Y Wang, J Nathans - Trends in molecular medicine, 2010 - cell.com
X Ye, Y Wang, J Nathans
Trends in molecular medicine, 2010cell.com
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 …
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.
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