Leopold, Stephanie A. and Zeilbeck, Ludwig F. and Weber, Gregor and Seitz, Roswitha and Boesl, Michael R. and Jaegle, Herbert and Fuchshofer, Rudolf and Tamm, Ernst R. and Ohlmann, Andreas (2017) Norrin protects optic nerve axons from degeneration in a mouse model of glaucoma. SCIENTIFIC REPORTS, 7: 14274. ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
Norrin is a secreted signaling molecule activating the Wnt/beta-catenin pathway. Since Norrin protects retinal neurons from experimental acute injury, we were interested to learn if Norrin attenuates chronic damage of retinal ganglion cells (RGC) and their axons in a mouse model of glaucoma. Transgenic mice overexpressing Norrin in the retina (Pax6-Norrin) were generated and crossed with DBA/2J mice with hereditary glaucoma and optic nerve axonal degeneration. One-year old DBA/2J/Pax6-Norrin animals had significantly more surviving optic nerve axons than their DBA/2J littermates. The protective effect correlated with an increase in insulin-like growth factor (IGF)-1 mRNA and an enhanced Akt phosphorylation in DBA/2J/Pax6-Norrin mice. Both mouse strains developed an increase in intraocular pressure during the second half of the first year and marked degenerative changes in chamber angle, ciliary body and iris structure. The degenerations were slightly attenuated in the chamber angle of DBA/2J/Pax6-Norrin mice, which showed a beta-catenin increase in the trabecular meshwork. We conclude that high levels of Norrin and the subsequent constitutive activation of Wnt/beta-catenin signaling in RGC protect from glaucomatous axonal damage via IGF-1 causing increased activity of PI3K-Akt signaling. Our results identify components of a protective signaling network preventing degeneration of optic nerve axons in glaucoma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RETINAL GANGLION-CELLS; GROWTH-FACTOR-I; WNT/BETA-CATENIN; DBA/2J MOUSE; VASCULAR DEVELOPMENT; TRABECULAR MESHWORK; PIGMENTARY GLAUCOMA; SIGNALING PATHWAY; NEURONAL SURVIVAL; MUTANT MICE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:19 |
| Last Modified: | 25 Feb 2019 15:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1982 |
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