Preserving Retinal Structure and Function with the Novel Nitroxide Antioxidant, DCTEIO
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Description
Oxidative stress is a major contributor to progressive neurodegenerative disease and may be a key target for the development of novel preventative and therapeutic strategies. Nitroxides have been successfully utilised to study changes in redox status (biological probes) and modulate radical-induced oxidative stress. This study investigates the efficacy of DCTEIO (5,6-dicarboxy-1,1,3,3-tetraethyllisoindolin-2-yloxyl), a stable, kinetically-persistent, nitroxide-based antioxidant, as a retinal neuroprotectant. The preservation of retinal function following an acute ischaemic/reperfusion (I/R) insult in the presence of DCTEIO was quantified by electroretinography (ERG). Inflammatory responses in retinal glia were analysed by GFAP and IBA-1 immunohistochemistry, and retinal integrity assessed by histology. A nitroxide probe combined with flow cytometry provided a rapid technique to assess oxidative stress and the mitigation offered by antioxidant compounds in cultured 661W photoreceptor cells. DCTEIO protected the retina from I/R-induced damage, maintaining retinal function. Histological analysis showed preservation of retinal integrity with reduced disruption and disorganisation of the inner and outer nuclear layers. I/R injury upregulated GFAP expression, indicative of retinal stress, which was significantly blunted by DCTEIO. The number of ‘activated’ microglia, particularly in the outer retina, in response to cellular stress was also significantly reduced by DCTEIO, potentially suggesting reduced inflammasome activation and cell death. DCTEIO mitigated oxidative stress in 661W retinal cell cultures, in a dose-dependent fashion. Together these findings demonstrate the potential of DCTEIO as a neuroprotective therapeutic for degenerative diseases of the CNS that involve an ROS-mediated component, including those of the retina e.g. age-related macular degeneration and glaucoma.
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ID Code: | 246201 | ||
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Item Type: | Contribution to Journal (Journal Article) | ||
Refereed: | Yes | ||
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Additional Information: | Funding Information: The team would like to thank Dr. Jason Tong for his contribution of flow cytometry pilot data to this study. This research was supported by the Clem Jones Foundation, the Cutmore Bequest to Bond University, Australian Research Council Centre of Excellence for Free Radical Chemistry and Biotechnology, and the Queensland Eye Institute Foundation. Open Access funding enabled and organized by CAUL and its Member Institutions. | ||
Measurements or Duration: | 18 pages | ||
Keywords: | Antioxidant, Ischemia, Neuroprotection, Nitroxide, Oxidative stress, Retina | ||
DOI: | 10.1007/s11064-023-03978-w | ||
ISSN: | 0364-3190 | ||
Pure ID: | 157161337 | ||
Divisions: | Current > Research Centres > Centre for Genomics and Personalised Health Current > QUT Faculties and Divisions > Faculty of Science Current > Schools > School of Chemistry & Physics Current > QUT Faculties and Divisions > Faculty of Health Current > Schools > School of Biomedical Sciences |
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Funding Information: | The team would like to thank Dr. Jason Tong for his contribution of flow cytometry pilot data to this study. This research was supported by the Clem Jones Foundation, the Cutmore Bequest to Bond University, Australian Research Council Centre of Excellence for Free Radical Chemistry and Biotechnology, and the Queensland Eye Institute Foundation. Open Access funding enabled and organized by CAUL and its Member Institutions. This research was supported by the Clem Jones Foundation, the Cutmore Bequest to Bond University, Australian Research Council Centre of Excellence for Free Radical Chemistry and Biotechnology, and the Queensland Eye Institute Foundation. The team would like to thank Dr. Jason Tong for his contribution of flow cytometry pilot data to this study. This research was supported by the Clem Jones Foundation, the Cutmore Bequest to Bond University, Australian Research Council Centre of Excellence for Free Radical Chemistry and Biotechnology, and the Queensland Eye Institute Foundation. | ||
Copyright Owner: | © 2023, The Author(s) | ||
Copyright Statement: | This work is covered by copyright. Unless the document is being made available under a Creative Commons Licence, you must assume that re-use is limited to personal use and that permission from the copyright owner must be obtained for all other uses. If the document is available under a Creative Commons License (or other specified license) then refer to the Licence for details of permitted re-use. It is a condition of access that users recognise and abide by the legal requirements associated with these rights. If you believe that this work infringes copyright please provide details by email to qut.copyright@qut.edu.au | ||
Deposited On: | 06 Feb 2024 06:13 | ||
Last Modified: | 05 Aug 2024 02:47 |
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