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Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model

BACKGROUND: In multiple sclerosis (MS), neurodegeneration is the main reason for chronic disability. Alpha-lipoic acid (LA) is a naturally occurring antioxidant which has recently been demonstrated to reduce the rate of brain atrophy in progressive MS. However, it remains uncertain if it is also ben...

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Autores principales: Dietrich, Michael, Helling, Niklas, Hilla, Alexander, Heskamp, Annemarie, Issberner, Andrea, Hildebrandt, Thomas, Kohne, Zippora, Küry, Patrick, Berndt, Carsten, Aktas, Orhan, Fischer, Dietmar, Hartung, Hans-Peter, Albrecht, Philipp
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840773/
https://www.ncbi.nlm.nih.gov/pubmed/29514678
http://dx.doi.org/10.1186/s12974-018-1111-y
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author Dietrich, Michael
Helling, Niklas
Hilla, Alexander
Heskamp, Annemarie
Issberner, Andrea
Hildebrandt, Thomas
Kohne, Zippora
Küry, Patrick
Berndt, Carsten
Aktas, Orhan
Fischer, Dietmar
Hartung, Hans-Peter
Albrecht, Philipp
author_facet Dietrich, Michael
Helling, Niklas
Hilla, Alexander
Heskamp, Annemarie
Issberner, Andrea
Hildebrandt, Thomas
Kohne, Zippora
Küry, Patrick
Berndt, Carsten
Aktas, Orhan
Fischer, Dietmar
Hartung, Hans-Peter
Albrecht, Philipp
author_sort Dietrich, Michael
collection PubMed
description BACKGROUND: In multiple sclerosis (MS), neurodegeneration is the main reason for chronic disability. Alpha-lipoic acid (LA) is a naturally occurring antioxidant which has recently been demonstrated to reduce the rate of brain atrophy in progressive MS. However, it remains uncertain if it is also beneficial in the early, more inflammatory-driven phases. As clinical studies are costly and time consuming, optic neuritis (ON) is often used for investigating neuroprotective or regenerative therapeutics. We aimed to investigate the prospect for success of a clinical ON trial using an experimental autoimmune encephalomyelitis-optic neuritis (EAE-ON) model with visual system readouts adaptable to a clinical ON trial. METHODS: Using an in vitro cell culture model for endogenous oxidative stress, we compared the neuroprotective capacity of racemic LA with the R/S-enantiomers and its reduced form. In vivo, we analyzed retinal neurodegeneration using optical coherence tomography (OCT) and the visual function by optokinetic response (OKR) in MOG(35–55)-induced EAE-ON in C57BL/6J mice. Ganglion cell counts, inflammation, and demyelination were assessed by immunohistological staining of retinae and optic nerves. RESULTS: All forms of LA provided equal neuroprotective capacities in vitro. In EAE-ON, prophylactic LA therapy attenuated the clinical EAE score and prevented the thinning of the inner retinal layer while therapeutic treatment was not protective on visual outcomes. CONCLUSIONS: A prophylactic LA treatment is necessary to protect from visual loss and retinal thinning in EAE-ON, suggesting that a clinical ON trial starting therapy after the onset of symptoms may not be successful. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-018-1111-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-58407732018-03-14 Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model Dietrich, Michael Helling, Niklas Hilla, Alexander Heskamp, Annemarie Issberner, Andrea Hildebrandt, Thomas Kohne, Zippora Küry, Patrick Berndt, Carsten Aktas, Orhan Fischer, Dietmar Hartung, Hans-Peter Albrecht, Philipp J Neuroinflammation Research BACKGROUND: In multiple sclerosis (MS), neurodegeneration is the main reason for chronic disability. Alpha-lipoic acid (LA) is a naturally occurring antioxidant which has recently been demonstrated to reduce the rate of brain atrophy in progressive MS. However, it remains uncertain if it is also beneficial in the early, more inflammatory-driven phases. As clinical studies are costly and time consuming, optic neuritis (ON) is often used for investigating neuroprotective or regenerative therapeutics. We aimed to investigate the prospect for success of a clinical ON trial using an experimental autoimmune encephalomyelitis-optic neuritis (EAE-ON) model with visual system readouts adaptable to a clinical ON trial. METHODS: Using an in vitro cell culture model for endogenous oxidative stress, we compared the neuroprotective capacity of racemic LA with the R/S-enantiomers and its reduced form. In vivo, we analyzed retinal neurodegeneration using optical coherence tomography (OCT) and the visual function by optokinetic response (OKR) in MOG(35–55)-induced EAE-ON in C57BL/6J mice. Ganglion cell counts, inflammation, and demyelination were assessed by immunohistological staining of retinae and optic nerves. RESULTS: All forms of LA provided equal neuroprotective capacities in vitro. In EAE-ON, prophylactic LA therapy attenuated the clinical EAE score and prevented the thinning of the inner retinal layer while therapeutic treatment was not protective on visual outcomes. CONCLUSIONS: A prophylactic LA treatment is necessary to protect from visual loss and retinal thinning in EAE-ON, suggesting that a clinical ON trial starting therapy after the onset of symptoms may not be successful. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-018-1111-y) contains supplementary material, which is available to authorized users. BioMed Central 2018-03-07 /pmc/articles/PMC5840773/ /pubmed/29514678 http://dx.doi.org/10.1186/s12974-018-1111-y Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Dietrich, Michael
Helling, Niklas
Hilla, Alexander
Heskamp, Annemarie
Issberner, Andrea
Hildebrandt, Thomas
Kohne, Zippora
Küry, Patrick
Berndt, Carsten
Aktas, Orhan
Fischer, Dietmar
Hartung, Hans-Peter
Albrecht, Philipp
Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model
title Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model
title_full Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model
title_fullStr Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model
title_full_unstemmed Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model
title_short Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model
title_sort early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840773/
https://www.ncbi.nlm.nih.gov/pubmed/29514678
http://dx.doi.org/10.1186/s12974-018-1111-y
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