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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-1\u03b1 (HIF1\u03b1) 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.<\/jats:p>","DOI":"10.3390\/ijms25053077","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T04:19:02Z","timestamp":1709785142000},"page":"3077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tissue Hypoxia and Associated Innate Immune Factors in Experimental Autoimmune Optic Neuritis"],"prefix":"10.3390","volume":"25","author":[{"given":"Zhiyuan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Marcoci","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hatice K\u00fcbra","family":"\u00d6zt\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK"},{"name":"Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleni","family":"Giama","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayse Gertrude","family":"Yenicelik","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5357-7562","authenticated-orcid":false,"given":"Ond\u0159ej","family":"Slana\u0159","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 12800 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Linington","sequence":"additional","affiliation":[{"name":"School of Infection and Immunity, The Sir Graeme Davies Building, Glasgow G12 8TA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roshni","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4408-7809","authenticated-orcid":false,"given":"Kenneth J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London WC1N 1PJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"key":"ref_1","first-page":"1236","article-title":"Optic Neuritis","volume":"25","author":"Bennett","year":"2019","journal-title":"Continuum"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/brain\/awu335","article-title":"Vision and vision-related outcome measures in multiple sclerosis","volume":"138","author":"Balcer","year":"2015","journal-title":"Brain"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S1474-4422(22)00187-9","article-title":"Optic neuritis and autoimmune optic neuropathies: Advances in diagnosis and treatment","volume":"22","author":"Bennett","year":"2023","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1001\/archopht.1993.01090060061023","article-title":"Optic neuritis treatment trial. 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