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Prophylactic nicotinamide treatment protects from rotenone-induced neurodegeneration by increasing mitochondrial content and volume
Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Oftalmiatrik. Department of Ophthalmology, University of Iceland, Reykjavik, Iceland.ORCID-id: 0000-0003-0218-4563
Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden.
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2024 (engelsk)Inngår i: Acta neuropathologica communications, E-ISSN 2051-5960, Vol. 12, nr 1, artikkel-id 37Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Leber’s hereditary optic neuropathy (LHON) is driven by mtDNA mutations affecting Complex I presenting as progressive retinal ganglion cell dysfunction usually in the absence of extra-ophthalmic symptoms. There are no long-term neuroprotective agents for LHON. Oral nicotinamide provides a robust neuroprotective effect against mitochondrial and metabolic dysfunction in other retinal injuries. We explored the potential for nicotinamide to protect mitochondria in LHON by modelling the disease in mice through intravitreal injection of the Complex I inhibitor rotenone. Using MitoV mice expressing a mitochondrial-tagged YFP in retinal ganglion cells we assessed mitochondrial morphology through super-resolution imaging and digital reconstruction. Rotenone induced Complex I inhibition resulted in retinal ganglion cell wide mitochondrial loss and fragmentation. This was prevented by oral nicotinamide treatment. Mitochondrial ultrastructure was quantified by transition electron microscopy, demonstrating a loss of cristae density following rotenone injection, which was also prevented by nicotinamide treatment. These results demonstrate that nicotinamide protects mitochondria during Complex I dysfunction. Nicotinamide has the potential to be a useful treatment strategy for LHON to limit retinal ganglion cell degeneration.

sted, utgiver, år, opplag, sider
BioMed Central (BMC), 2024. Vol. 12, nr 1, artikkel-id 37
Emneord [en]
Mitochondria, Neurodegeneration, Nicotinamide, Optic nerve, Retina, Retina ganglion cells
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Identifikatorer
URN: urn:nbn:se:umu:diva-222236DOI: 10.1186/s40478-024-01724-zISI: 1176539900001PubMedID: 38429841Scopus ID: 2-s2.0-85186470382OAI: oai:DiVA.org:umu-222236DiVA, id: diva2:1845261
Forskningsfinansiär
Swedish Research Council, 2022–00799Karolinska InstituteStiftelsen Kronprinsessan Margaretas arbetsnämnd för synskadadeTilgjengelig fra: 2024-03-18 Laget: 2024-03-18 Sist oppdatert: 2024-03-18bibliografisk kontrollert

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