Retinal alpha-synuclein accumulation correlates with retinal dysfunction and structural thinning in the A53T mouse model of Parkinson’s disease
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 overexpressi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1146979/full |
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| author | Katie K. N. Tran Vickie H. Y. Wong Anh Hoang David I. Finkelstein Bang V. Bui Christine T. O. Nguyen |
| author_facet | Katie K. N. Tran Vickie H. Y. Wong Anh Hoang David I. Finkelstein Bang V. Bui Christine T. O. Nguyen |
| author_sort | Katie K. N. Tran |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T14:18:32Z |
| format | Article |
| id | doaj.art-7914c93654a74f62859b382945c94c8a |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-09T14:18:32Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-7914c93654a74f62859b382945c94c8a2023-05-05T05:17:30ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-05-011710.3389/fnins.2023.11469791146979Retinal alpha-synuclein accumulation correlates with retinal dysfunction and structural thinning in the A53T mouse model of Parkinson’s diseaseKatie K. N. Tran0Vickie H. Y. Wong1Anh Hoang2David I. Finkelstein3Bang V. Bui4Christine T. O. Nguyen5Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, AustraliaThe Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, AustraliaDepartment of Optometry and Vision Sciences, The University of Melbourne, Parkville, VIC, AustraliaAbnormal 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.https://www.frontiersin.org/articles/10.3389/fnins.2023.1146979/fullA53Talpha-synucleinParkinson’s diseaseretinaelectroretinographyoptical coherence tomography |
| spellingShingle | Katie K. N. Tran Vickie H. Y. Wong Anh Hoang David I. Finkelstein Bang V. Bui Christine T. O. Nguyen Retinal alpha-synuclein accumulation correlates with retinal dysfunction and structural thinning in the A53T mouse model of Parkinson’s disease Frontiers in Neuroscience A53T alpha-synuclein Parkinson’s disease retina electroretinography optical coherence tomography |
| title | Retinal alpha-synuclein accumulation correlates with retinal dysfunction and structural thinning in the A53T mouse model of Parkinson’s disease |
| title_full | Retinal alpha-synuclein accumulation correlates with retinal dysfunction and structural thinning in the A53T mouse model of Parkinson’s disease |
| title_fullStr | Retinal alpha-synuclein accumulation correlates with retinal dysfunction and structural thinning in the A53T mouse model of Parkinson’s disease |
| title_full_unstemmed | Retinal alpha-synuclein accumulation correlates with retinal dysfunction and structural thinning in the A53T mouse model of Parkinson’s disease |
| title_short | Retinal alpha-synuclein accumulation correlates with retinal dysfunction and structural thinning in the A53T mouse model of Parkinson’s disease |
| title_sort | retinal alpha synuclein accumulation correlates with retinal dysfunction and structural thinning in the a53t mouse model of parkinson s disease |
| topic | A53T alpha-synuclein Parkinson’s disease retina electroretinography optical coherence tomography |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1146979/full |
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