Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783304639859392512 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5840773 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT dietrichmichael earlyalphalipoicacidtherapyprotectsfromdegenerationoftheinnerretinallayersandvisionlossinanexperimentalautoimmuneencephalomyelitisopticneuritismodel AT hellingniklas earlyalphalipoicacidtherapyprotectsfromdegenerationoftheinnerretinallayersandvisionlossinanexperimentalautoimmuneencephalomyelitisopticneuritismodel AT hillaalexander earlyalphalipoicacidtherapyprotectsfromdegenerationoftheinnerretinallayersandvisionlossinanexperimentalautoimmuneencephalomyelitisopticneuritismodel AT heskampannemarie earlyalphalipoicacidtherapyprotectsfromdegenerationoftheinnerretinallayersandvisionlossinanexperimentalautoimmuneencephalomyelitisopticneuritismodel AT issbernerandrea earlyalphalipoicacidtherapyprotectsfromdegenerationoftheinnerretinallayersandvisionlossinanexperimentalautoimmuneencephalomyelitisopticneuritismodel AT hildebrandtthomas earlyalphalipoicacidtherapyprotectsfromdegenerationoftheinnerretinallayersandvisionlossinanexperimentalautoimmuneencephalomyelitisopticneuritismodel AT kohnezippora earlyalphalipoicacidtherapyprotectsfromdegenerationoftheinnerretinallayersandvisionlossinanexperimentalautoimmuneencephalomyelitisopticneuritismodel AT kurypatrick earlyalphalipoicacidtherapyprotectsfromdegenerationoftheinnerretinallayersandvisionlossinanexperimentalautoimmuneencephalomyelitisopticneuritismodel AT berndtcarsten earlyalphalipoicacidtherapyprotectsfromdegenerationoftheinnerretinallayersandvisionlossinanexperimentalautoimmuneencephalomyelitisopticneuritismodel AT aktasorhan earlyalphalipoicacidtherapyprotectsfromdegenerationoftheinnerretinallayersandvisionlossinanexperimentalautoimmuneencephalomyelitisopticneuritismodel AT fischerdietmar earlyalphalipoicacidtherapyprotectsfromdegenerationoftheinnerretinallayersandvisionlossinanexperimentalautoimmuneencephalomyelitisopticneuritismodel AT hartunghanspeter earlyalphalipoicacidtherapyprotectsfromdegenerationoftheinnerretinallayersandvisionlossinanexperimentalautoimmuneencephalomyelitisopticneuritismodel AT albrechtphilipp earlyalphalipoicacidtherapyprotectsfromdegenerationoftheinnerretinallayersandvisionlossinanexperimentalautoimmuneencephalomyelitisopticneuritismodel |