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The Norrin/Frizzled4 signaling pathway in retinal vascular development and disease Ye X; Wang Y; Nathans JTrends Mol Med 2010[Sep]; 16 (9): 417-25Disorders 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.|*Signal Transduction[MESH]|Animals[MESH]|Frizzled Receptors/genetics/*metabolism[MESH]|Humans[MESH]|Nerve Tissue Proteins/genetics/*metabolism[MESH]|Retinal Neovascularization/genetics/*metabolism[MESH]|Retinal Vein/*growth & development/metabolism[MESH] |
