Norrin Protects Retinal Ganglion Cells from Excitotoxic Damage via the Induction of Leukemia Inhibitory Factor

Kassumeh, Stefan and Leopold, Stephanie and Fuchshofer, Rudolf and Thomas, Carina N. and Priglinger, Siegfried G. and Tamm, Ernst R. and Ohlmann, Andreas (2020) Norrin Protects Retinal Ganglion Cells from Excitotoxic Damage via the Induction of Leukemia Inhibitory Factor. CELLS, 9 (2): 277. ISSN , 2073-4409

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Abstract

Purpose: To investigate whether and how leukemia inhibitory factor (Lif) is involved in mediating the neuroprotective effects of Norrin on retinal ganglion cells (RGC) following excitotoxic damage. Norrin is a secreted protein that protects RGC from N-methyl-d-aspartate (NMDA)-mediated excitotoxic damage, which is accompanied by increased expression of protective factors such as Lif, Edn2 and Fgf2. Methods: Lif-deficient mice were injected with NMDA in one eye and NMDA plus Norrin into the other eye. RGC damage was investigated and quantified by TUNEL labeling 24 h after injection. Retinal mRNA expression was analyzed by quantitative real-time polymerase chain reaction following retinal treatment. Results: After intravitreal injection of NMDA and Norrin in wild-type mice approximately 50% less TUNEL positive cells were observed in the RGC layer when compared to NMDA-treated littermates, an effect which was lost in Lif-deficient mice. The mRNA expression for Gfap, a marker for Muller cell gliosis, as well as Edn2 and Fgf2 was induced in wild-type mice following NMDA/Norrin treatment but substantially blocked in Lif-deficient mice. Conclusions: Norrin mediates its protective properties on RGC via Lif, which is required to enhance Muller cell gliosis and to induce protective factors such as Edn2 or Fgf2.

Item Type: Article
Uncontrolled Keywords: SIGNALING PATHWAY; WNT/BETA-CATENIN; GROWTH-FACTORS; MULLER CELLS; PHOTORECEPTORS; RECEPTOR; CNTF; NMDA; VASCULATURE; MAINTENANCE; Lif; retinal ganglion cells; neuroprotection; excitotoxic damage; NMDA; apoptosis; Norrin; Wnt/beta-catenin signaling
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie > Prof. Dr. Ernst Tamm
Depositing User: Dr. Gernot Deinzer
Date Deposited: 30 Mar 2021 10:38
Last Modified: 30 Mar 2021 10:38
URI: https://pred.uni-regensburg.de/id/eprint/45175

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