title: The Norrin/Frizzled4 signaling pathway in retinal vascular development and disease.
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.
authors.affiliation: Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Ye
authors.forename: Yanshu
authors.initials: Y
authors.lastname: Wang
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nathans
mesh_terms: D000818:Animals; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D015861:Retinal Neovascularization / Q000235:genetics / Q000378:metabolism*; D012169:Retinal Vein / Q000254:growth & development* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051157:Frizzled Receptors; D009419:Nerve Tissue Proteins