Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Progressive Retinal and Optic Nerve Damage in a Mouse Model of Spontaneous Opticospinal Encephalomyelitis

Petrikowski, Laura ; Reinehr, Sabrina ; Haupeltshofer, Steffen LU ; Deppe, Leonie ; Graz, Florian ; Kleiter, Ingo ; Dick, H. Burkhard ; Gold, Ralf ; Faissner, Simon and Joachim, Stephanie C. (2022) In Frontiers in Immunology 12.
Abstract

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... (More)

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 Pou4f1 mRNA expression in OSE retinas. RT-qPCR revealed an elevation of microglia markers and the cytokines Tnfa and 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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
complement system, demyelination, inflammation, microglia, myelin oligodendrocyte glycoprotein antibodies (MOG-IgG), Neuromyelitis optica, optic nerve, retinal ganglion cells
in
Frontiers in Immunology
volume
12
article number
759389
publisher
Frontiers Media S. A.
external identifiers
  • pmid:35140707
  • scopus:85124185294
ISSN
1664-3224
DOI
10.3389/fimmu.2021.759389
language
English
LU publication?
no
additional info
Publisher Copyright: Copyright © 2022 Petrikowski, Reinehr, Haupeltshofer, Deppe, Graz, Kleiter, Dick, Gold, Faissner and Joachim.
id
b9025ba5-4291-401c-84f5-dfd4ba8d14c3
date added to LUP
2026-02-04 15:53:13
date last changed
2026-02-04 15:54:28
@article{b9025ba5-4291-401c-84f5-dfd4ba8d14c3,
  abstract     = {{<p>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 Pou4f1 mRNA expression in OSE retinas. RT-qPCR revealed an elevation of microglia markers and the cytokines Tnfa and 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.</p>}},
  author       = {{Petrikowski, Laura and Reinehr, Sabrina and Haupeltshofer, Steffen and Deppe, Leonie and Graz, Florian and Kleiter, Ingo and Dick, H. Burkhard and Gold, Ralf and Faissner, Simon and Joachim, Stephanie C.}},
  issn         = {{1664-3224}},
  keywords     = {{complement system; demyelination; inflammation; microglia; myelin oligodendrocyte glycoprotein antibodies (MOG-IgG); Neuromyelitis optica; optic nerve; retinal ganglion cells}},
  language     = {{eng}},
  month        = {{01}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Progressive Retinal and Optic Nerve Damage in a Mouse Model of Spontaneous Opticospinal Encephalomyelitis}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2021.759389}},
  doi          = {{10.3389/fimmu.2021.759389}},
  volume       = {{12}},
  year         = {{2022}},
}