Ohlmann, Andreas and Tamm, Ernst R. (2012) Norrin: Molecular and functional properties of an angiogenic and neuroprotective growth factor. PROGRESS IN RETINAL AND EYE RESEARCH, 31 (3). pp. 243-257. ISSN 1350-9462, 1873-1635
Full text not available from this repository. (Request a copy)Abstract
Norrin is a secreted signaling molecule with structural and functional characteristics of an autocrine and/or paracrine acting growth factor. In the eye, Norrin is constitutively expressed in Muller cells. Norrin specifically binds to Frizzled-4 receptors and activates the canonical Wnt/beta-catenin signaling pathway that is profoundly enhanced when Tspan12 is present at the Norrin/Frizzled-4 receptor complex. In the absence of Norrin or Frizzled-4, intraretinal capillaries are not formed during developmental angiogenesis. As a result there is considerable evidence that Norrin and Frizzled-4 are part of an essential signaling system that controls the formation of the retinal vasculature during eye development. Intriguingly, Norrin promotes vessel regrowth and induces the formation of intraretinal capillaries following oxygen-induced retinopathy in mice, an animal model of retinopathy of prematurity. Moreover, Norrin has pronounced neuroprotective properties on retinal ganglion cells (RGC) with the distinct potential to decrease the damaging effects of excitotoxic NMDA-induced RGC injury. The neuroprotective effects of Norrin similarly involve an activation of Wnt/beta-catenin signaling and the subsequent induction of neuroprotective growth factor synthesis in Muller cells, such as that of fibroblast growth factor-2 (FGF2) or ciliary neurotrophic factor (CNTF). Overall, Norrin and the molecules involved in its signaling pathway appear to be promising targets to develop strategies that induce intraretinal vessel formation in patients suffering from ischemic retinopathies, or that increase RGC survival in glaucoma. (c) 2012 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FAMILIAL EXUDATIVE VITREORETINOPATHY; BLOOD-BRAIN-BARRIER; RETINAL VASCULAR DEVELOPMENT; RECEPTOR-RELATED PROTEIN-5; CELL INTRAOCULAR IMPLANTS; DISEASE GENE; SIGNALING PATHWAY; MOUSE MODEL; BILATERAL PSEUDOTUMOUR; MISSENSE MUTATIONS; Angiogenesis; Neuroprotection; Wnt; beta-Catenin; Retinopathy of prematurity; Glaucoma; Muller cells |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie > Prof. Dr. Ernst Tamm |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 May 2020 11:45 |
| Last Modified: | 14 May 2020 11:45 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18793 |
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