Progressive retinal and optic nerve damage in a mouse model of spontaneous opticospinal encephalomyelitis
- Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-antibody-associated disease (MOGAD) are antibody mediated CNS disorders mostly affecting the optic nerve and spinal cord with potential severe impact on the visual pathway. Here, we investigated inflammation and degeneration of the visual system in a spontaneous encephalomyelitis animal model. We used double-transgenic (2D2/Th) mice which develop a spontaneous opticospinal encephalomyelitis (OSE). Retinal morphology and its function were evaluated via spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG) in 6- and 8-week-old mice. Immunohistochemistry of retina and optic nerve and examination of the retina via RT-qPCR were performed using markers for inflammation, immune cells and the complement pathway. OSE mice showed clinical signs of encephalomyelitis with an incidence of 75% at day 38. A progressive retinal thinning was detected in OSE mice via SD-OCT. An impairment in photoreceptor signal transmission occurred. This was accompanied by cellular infiltration and demyelination of optic nerves. The number of microglia/macrophages was increased in OSE optic nerves and retinas. Analysis of the retina revealed a reduced retinal ganglion cell number and downregulated \(\it Pou4f1\) mRNA expression in OSE retinas. RT-qPCR revealed an elevation of microglia markers and the cytokines \(\it Tnfa\) and \(\it Tgfb\). We also documented an upregulation of the complement system via the classical pathway. In summary, we describe characteristics of inflammation and degeneration of the visual system in a spontaneous encephalomyelitis model, characterized by coinciding inflammatory and degenerative mechanisms in both retina and optic nerve with involvement of the complement system.
Author: | Laura PetrikowskiGND, Sabrina ReinehrORCiDGND, Steffen HaupeltshoferGND, Leonie DeppeGND, Florian GrazGND, Ingo Wolfram KleiterGND, Burkhard DickORCiDGND, Ralf GoldORCiDGND, Simon Raoul FaissnerORCiDGND, Stephanie Christine JoachimORCiDGND |
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URN: | urn:nbn:de:hbz:294-86817 |
DOI: | https://doi.org/10.3389/fimmu.2021.759389 |
Parent Title (English): | Frontiers in immunology |
Publisher: | Frontiers Media |
Place of publication: | Lausanne |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2022/03/08 |
Date of first Publication: | 2022/01/24 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds Neuromyelitis optica; complement system; demyelination; inflammation; microglia; myelin oligodendrocyte glycoprotein antibodies (MOG-IgG); optic nerve; retinal ganglion cells |
Volume: | 12 |
Issue: | Article 759389 |
First Page: | 759389-1 |
Last Page: | 759389-18 |
Note: | Article Processing Charge funded by the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Katholisches Klinikum Bochum, Neurologie |
open_access (DINI-Set): | open_access |
faculties: | Medizinische Fakultät |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |