Retinal alpha-synuclein accumulation correlates with retinal dysfunction and structural thinning in the A53T mouse model of Parkinson's disease.
| Autor: | Tran KKN; Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, Australia., Wong VHY; Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, Australia., Hoang A; Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, Australia., Finkelstein DI; The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia., Bui BV; Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, Australia., Nguyen CTO; Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, Australia. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in neuroscience [Front Neurosci] 2023 May 05; Vol. 17, pp. 1146979. Date of Electronic Publication: 2023 May 05 (Print Publication: 2023). |
| DOI: | 10.3389/fnins.2023.1146979 |
| Abstrakt: | Abnormal alpha-synuclein (α-SYN) protein deposition has long been recognized as one of the pathological hallmarks of Parkinson's disease's (PD). This study considers the potential utility of PD retinal biomarkers by investigating retinal changes in a well characterized PD model of α-SYN overexpression and how these correspond to the presence of retinal α-SYN. Transgenic A53T homozygous (HOM) mice overexpressing human α-SYN and wildtype (WT) control littermates were assessed at 4, 6, and 14 months of age (male and female, n = 15-29 per group). In vivo retinal function (electroretinography, ERG) and structure (optical coherence tomography, OCT) were recorded, and retinal immunohistochemistry and western blot assays were performed to examine retinal α-SYN and tyrosine hydroxylase. Compared to WT controls, A53T mice exhibited reduced light-adapted (cone photoreceptor and bipolar cell amplitude, p < 0.0001) ERG responses and outer retinal thinning (outer plexiform layer, outer nuclear layer, p < 0.0001) which correlated with elevated levels of α-SYN. These retinal signatures provide a high throughput means to study α-SYN induced neurodegeneration and may be useful in vivo endpoints for PD drug discovery. Competing Interests: CN and BB are joint investigators on an Australian Research Council Linkage grant LP160100126 with AstraZeneca Neuroscience and Biogen Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Tran, Wong, Hoang, Finkelstein, Bui and Nguyen.) |
| Databáze: | MEDLINE |
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