Characterization of retinal function and structure in the MPTP murine model of Parkinson's disease.

Autor: Tran KKN; Ocular Biomarkers Laboratory, Department of Optometry and Vision Sciences, University of Melbourne, Parkville, VIC, 3010, Australia., Wong VHY; Ocular Biomarkers Laboratory, Department of Optometry and Vision Sciences, University of Melbourne, Parkville, VIC, 3010, Australia., Lim JKH; Ocular Biomarkers Laboratory, Department of Optometry and Vision Sciences, University of Melbourne, Parkville, VIC, 3010, Australia.; Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA, 5042, Australia., Shahandeh A; Ocular Biomarkers Laboratory, Department of Optometry and Vision Sciences, University of Melbourne, Parkville, VIC, 3010, Australia., Hoang A; Ocular Biomarkers Laboratory, Department of Optometry and Vision Sciences, University of Melbourne, Parkville, VIC, 3010, Australia., Finkelstein DI; Parkinson's Disease Laboratory, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, 3010, Australia., Bui BV; Ocular Biomarkers Laboratory, Department of Optometry and Vision Sciences, University of Melbourne, Parkville, VIC, 3010, Australia., Nguyen CTO; Ocular Biomarkers Laboratory, Department of Optometry and Vision Sciences, University of Melbourne, Parkville, VIC, 3010, Australia. christine.nguyen@unimelb.edu.au.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 May 09; Vol. 12 (1), pp. 7610. Date of Electronic Publication: 2022 May 09.
DOI: 10.1038/s41598-022-11495-z
Abstrakt: In addition to well characterized motor symptoms, visual disturbances are increasingly recognized as an early manifestation in Parkinson's disease (PD). A better understanding of the mechanisms underlying these changes would facilitate the development of vision tests which can be used as preclinical biomarkers to support the development of novel therapeutics for PD. This study aims to characterize the retinal phenotype of a mouse model of dopaminergic dysfunction and to examine whether these changes are reversible with levodopa treatment. We use a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to characterize the neurotoxic effects of MPTP on in vivo retinal function (electroretinography, ERG), retinal structure (optical coherence tomography, OCT) and retinal dopaminergic cell number (tyrosine hydroxylase immunohistochemistry, IHC) at two time points (21 and 45 days) post MPTP model induction. We also investigate the effect of levodopa (L-DOPA) as a proof-of-principle chronic intervention against MPTP-induced changes in the retina. We show that MPTP decreases dopaminergic amacrine cell number (9%, p < 0.05) and that a component of the ERG that involves these cells, in particular oscillatory potential (OP) peak timing, was significantly delayed at Day 45 (7-13%, p < 0.01). This functional deficit was paralleled by outer plexiform layer (OPL) thinning (p < 0.05). L-DOPA treatment ameliorated oscillatory potential deficits (7-13%, p < 0.001) in MPTP animals. Our data suggest that the MPTP toxin slows the timing of inner retinal feedback circuits related to retinal dopaminergic pathways which mirrors findings from humans with PD. It also indicates that the MPTP model causes structural thinning of the outer retinal layer on OCT imaging that is not ameliorated with L-DOPA treatment. Together, these non-invasive measures serve as effective biomarkers for PD diagnosis as well as for quantifying the effect of therapy.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz: