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

Autor: Cruz-Herranz A; Division of Neuroimmunology and Glial Biology, Department of Neurology, University of California, San Francisco, San Francisco, USA., Dietrich M; Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Hilla AM; Department of Cell Physiology, Faculty of Biology and Biotechnology, Ruhr-University Bochum, Bochum, Germany., Yiu HH; Division of Neuroimmunology and Glial Biology, Department of Neurology, University of California, San Francisco, San Francisco, USA., Levin MH; Department of Ophthalmology, University of California, San Francisco, San Francisco, USA.; Department of Ophthalmology, Palo Alto Medical Foundation, Palo Alto, CA, USA., Hecker C; Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Issberner A; Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Hallenberger A; Institute of Anatomy II, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Cordano C; Division of Neuroimmunology and Glial Biology, Department of Neurology, University of California, San Francisco, San Francisco, USA., Lehmann-Horn K; Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Balk LJ; Department of Neurology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Aktas O; Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Ingwersen J; Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., von Gall C; Institute of Anatomy II, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Hartung HP; Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany., Zamvil SS; Division of Neuroimmunology and Glial Biology, Department of Neurology, University of California, San Francisco, San Francisco, USA.; Program in Immunology, University of California, San Francisco, San Francisco, USA., Fischer D; Department of Cell Physiology, Faculty of Biology and Biotechnology, Ruhr-University Bochum, Bochum, Germany., Albrecht P; Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany. phil.albrecht@gmail.com., Green AJ; Division of Neuroimmunology and Glial Biology, Department of Neurology, University of California, San Francisco, San Francisco, USA. agreen@ucsf.edu.; Department of Ophthalmology, University of California, San Francisco, San Francisco, USA. agreen@ucsf.edu.
Jazyk: angličtina
Zdroj: Journal of neuroinflammation [J Neuroinflammation] 2019 Nov 04; Vol. 16 (1), pp. 203. Date of Electronic Publication: 2019 Nov 04.
DOI: 10.1186/s12974-019-1583-4
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje