Dopaminergic Retinal Cell Loss and Visual Dysfunction in Parkinson Disease
© 2020 American Neurological Association..
OBJECTIVE: Considering the demonstrated implication of the retina in Parkinson disease (PD) pathology and the importance of dopaminergic cells in this tissue, we aimed to analyze the state of the dopaminergic amacrine cells and some of their main postsynaptic neurons in the retina of PD.
METHODS: Using immunohistochemistry and confocal microscopy, we evaluated morphology, number, and synaptic connections of dopaminergic cells and their postsynaptic cells, AII amacrine and melanopsin-containing retinal ganglion cells, in control and PD eyes from human donors.
RESULTS: In PD, dopaminergic amacrine cell number was reduced between 58% and 26% in different retinal regions, involving a decline in the number of synaptic contacts with AII amacrine cells (by 60%) and melanopsin cells (by 35%). Despite losing their main synaptic input, AII cells were not reduced in number, but they showed cellular alterations compromising their adequate function: (1) a loss of mitochondria inside their lobular appendages, which may indicate an energetic failure; and (2) a loss of connexin 36, suggesting alterations in the AII coupling and in visual signal transmission from the rod pathway.
INTERPRETATION: The dopaminergic system impairment and the affection of the rod pathway through the AII cells may explain and be partially responsible for the reduced contrast sensitivity or electroretinographic response described in PD. Also, dopamine reduction and the loss of synaptic contacts with melanopsin cells may contribute to the melanopsin retinal ganglion cell loss previously described and to the disturbances in circadian rhythm and sleep reported in PD patients. These data support the idea that the retina reproduces brain neurodegeneration and is highly involved in PD pathology. ANN NEUROL 2020;88:893-906.
Errataetall: |
CommentIn: Ann Neurol. 2021 Feb;89(2):421-422. - PMID 33236378 |
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Medienart: |
E-Artikel |
Erscheinungsjahr: |
2020 |
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Erschienen: |
2020 |
Enthalten in: |
Zur Gesamtaufnahme - volume:88 |
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Enthalten in: |
Annals of neurology - 88(2020), 5 vom: 02. Nov., Seite 893-906 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Ortuño-Lizarán, Isabel [VerfasserIn] |
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Links: |
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Themen: |
Connexins |
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Anmerkungen: |
Date Completed 14.12.2020 Date Revised 13.12.2023 published: Print-Electronic CommentIn: Ann Neurol. 2021 Feb;89(2):421-422. - PMID 33236378 Citation Status MEDLINE |
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doi: |
10.1002/ana.25897 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM314539441 |
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500 | |a CommentIn: Ann Neurol. 2021 Feb;89(2):421-422. - PMID 33236378 | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2020 American Neurological Association. | ||
520 | |a OBJECTIVE: Considering the demonstrated implication of the retina in Parkinson disease (PD) pathology and the importance of dopaminergic cells in this tissue, we aimed to analyze the state of the dopaminergic amacrine cells and some of their main postsynaptic neurons in the retina of PD | ||
520 | |a METHODS: Using immunohistochemistry and confocal microscopy, we evaluated morphology, number, and synaptic connections of dopaminergic cells and their postsynaptic cells, AII amacrine and melanopsin-containing retinal ganglion cells, in control and PD eyes from human donors | ||
520 | |a RESULTS: In PD, dopaminergic amacrine cell number was reduced between 58% and 26% in different retinal regions, involving a decline in the number of synaptic contacts with AII amacrine cells (by 60%) and melanopsin cells (by 35%). Despite losing their main synaptic input, AII cells were not reduced in number, but they showed cellular alterations compromising their adequate function: (1) a loss of mitochondria inside their lobular appendages, which may indicate an energetic failure; and (2) a loss of connexin 36, suggesting alterations in the AII coupling and in visual signal transmission from the rod pathway | ||
520 | |a INTERPRETATION: The dopaminergic system impairment and the affection of the rod pathway through the AII cells may explain and be partially responsible for the reduced contrast sensitivity or electroretinographic response described in PD. Also, dopamine reduction and the loss of synaptic contacts with melanopsin cells may contribute to the melanopsin retinal ganglion cell loss previously described and to the disturbances in circadian rhythm and sleep reported in PD patients. These data support the idea that the retina reproduces brain neurodegeneration and is highly involved in PD pathology. ANN NEUROL 2020;88:893-906 | ||
650 | 4 | |a Journal Article | |
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650 | 4 | |a Research Support, Non-U.S. Gov't | |
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700 | 1 | |a Beach, Thomas G |e verfasserin |4 aut | |
700 | 1 | |a Adler, Charles H |e verfasserin |4 aut | |
700 | 1 | |a Cuenca, Nicolás |e verfasserin |4 aut | |
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