Monitoring retinal changes with optical coherence tomography predicts neuronal loss in experimental autoimmune encephalomyelitis

Background Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental a...

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Published in:Journal of neuroinflammation Vol. 16; no. 1; pp. 203 - 17
Main Authors: Cruz-Herranz, Andrés, Dietrich, Michael, Hilla, Alexander M., Yiu, Hao H., Levin, Marc H., Hecker, Christina, Issberner, Andrea, Hallenberger, Angelika, Cordano, Christian, Lehmann-Horn, Klaus, Balk, Lisanne J., Aktas, Orhan, Ingwersen, Jens, von Gall, Charlotte, Hartung, Hans-Peter, Zamvil, Scott S., Fischer, Dietmar, Albrecht, Philipp, Green, Ari J.
Format: Journal Article
Language:English
Published: London BioMed Central 04.11.2019
BioMed Central Ltd
BMC
Subjects:
Animals
Best practices
Biomedical and Life Sciences
Biomedicine
Comparative analysis
Encephalomyelitis
Encephalomyelitis, Autoimmune, Experimental - pathology
Experimental autoimmune encephalomyelitis
Experimental optic neuritis
Ganglion cysts
House mouse
Immunization
Immunology
Mice
Mice, Inbred C57BL
Multiple sclerosis
Myelin proteins
Nerve Degeneration - pathology
Neuritis
Neurobiology
Neurodegeneration
Neurology
Neurons
Neurons - pathology
Neurosciences
Optic neuritis
Optical coherence tomography
Optokinetic response
Peptides
Retina - pathology
Rodents
Tomography
Tomography, Optical Coherence - methods
Germany
Experimental autoimmune encephalomyelitis
Multiple sclerosis
Optical coherence tomography
Neurodegeneration
Experimental optic neuritis
Optokinetic response
ISSN:1742-2094, 1742-2094
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Summary:Background Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. Methods Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG 35–55 ) or with bovine myelin basic protein (MBP), in TCR 2D2 mice immunized with MOG 35–55 , and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP 139–151 ). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. Results Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG 35–55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG 35–55 -immunized TCR 2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. Conclusions Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG 35–55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE.
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ISSN:1742-2094
1742-2094
DOI:10.1186/s12974-019-1583-4