Yang, Zhiyuan;
Marcoci, Cristina;
Öztürk, Hatice Kübra;
Giama, Eleni;
Yenicelik, Ayse Gertrude;
Slanař, Ondřej;
Linington, Christopher;
... Smith, Kenneth J; + view all
(2024)
Tissue Hypoxia and Associated Innate Immune Factors in Experimental Autoimmune Optic Neuritis.
International Journal of Molecular Sciences
, 25
(5)
, Article 3077. 10.3390/ijms25053077.
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Abstract
Visual loss in acute optic neuritis is typically attributed to axonal conduction block due to inflammatory demyelination, but the mechanisms remain unclear. Recent research has highlighted tissue hypoxia as an important cause of neurological deficits and tissue damage in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) and, here, we examine whether the optic nerves are hypoxic in experimental optic neuritis induced in Dark Agouti rats. At both the first and second peaks of disease expression, inflamed optic nerves labelled significantly for tissue hypoxia (namely, positive for hypoxia inducible factor-1α (HIF1α) and intravenously administered pimonidazole). Acutely inflamed nerves were also labelled significantly for innate markers of oxidative and nitrative stress and damage, including superoxide, nitric oxide and 3-nitrotyrosine. The density and diameter of capillaries were also increased. We conclude that in acute optic neuritis, the optic nerves are hypoxic and come under oxidative and nitrative stress and damage. Tissue hypoxia can cause mitochondrial failure and thus explains visual loss due to axonal conduction block. Tissue hypoxia can also induce a damaging oxidative and nitrative environment. The findings indicate that treatment to prevent tissue hypoxia in acute optic neuritis may help to restore vision and protect from damaging reactive oxygen and nitrogen species.
| Type: | Article |
|---|---|
| Title: | Tissue Hypoxia and Associated Innate Immune Factors in Experimental Autoimmune Optic Neuritis |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/ijms25053077 |
| Publisher version: | https://doi.org/10.3390/ijms25053077 |
| Language: | English |
| Additional information: | Copyright © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
| Keywords: | oxidative stress; superoxide; nitric oxide; peroxynitrite; hypoxia inducible factor-1α; multiple sclerosis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10189476 |
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