Starburst amacrine cells, involved in visual motion perception, loose their synaptic input from dopaminergic amacrine cells and degenerate in Parkinson’s disease patients
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|Starburst amacrine cells, involved in visual motion perception, loose their synaptic input from dopaminergic amacrine cells and degenerate in Parkinson’s disease patients
|Sánchez-Sáez, Xavier | Ortuño-Lizarán, Isabel | Sánchez-Castillo, Carla | Lax, Pedro | Cuenca, Nicolás
|Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS)
|Center, Department or Service:
|Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología | Universidad de Alicante. Instituto Multidisciplinar para el Estudio del Medio "Ramón Margalef"
|Parkinson’s disease | Retinal neurodegeneration | Human retina | ChAT amacrine cells | Dopaminergic amacrine cells
|Translational Neurodegeneration. 2023, 12:17. https://doi.org/10.1186/s40035-023-00348-y
|Background The main clinical symptoms characteristic of Parkinson’s disease (PD) are bradykinesia, tremor, and other motor deficits. However, non-motor symptoms, such as visual disturbances, can be identified at early stages of the disease. One of these symptoms is the impairment of visual motion perception. Hence, we sought to determine if the starburst amacrine cells, which are the main cellular type involved in motion direction selectivity, are degenerated in PD and if the dopaminergic system is related to this degeneration. Methods Human eyes from control (n = 10) and PD (n = 9) donors were available for this study. Using immunohistochemistry and confocal microscopy, we quantified starburst amacrine cell density (choline acetyltransferase [ChAT]-positive cells) and the relationship between these cells and dopaminergic amacrine cells (tyrosine hydroxylase-positive cells and vesicular monoamine transporter-2-positive presynapses) in cross-sections and wholemount retinas. Results First, we found two different ChAT amacrine populations in the human retina that presented different ChAT immunoreactivity intensity and different expression of calcium-binding proteins. Both populations are affected in PD and their density is reduced compared to controls. Also, we report, for the first time, synaptic contacts between dopaminergic amacrine cells and ChAT-positive cells in the human retina. We found that, in PD retinas, there is a reduction of the dopaminergic synaptic contacts into ChAT cells. Conclusions Taken together, this work indicates degeneration of starburst amacrine cells in PD related to dopaminergic degeneration and that dopaminergic amacrine cells could modulate the function of starburst amacrine cells. Since motion perception circuitries are affected in PD, their assessment using visual tests could provide new insights into the diagnosis of PD.
|We acknowledge financial support from the Ministerio de Ciencia e Innovación (FEDER-PID 2019-106230RB-I00), Ministerio de Universidades (FPU16/04114), Instituto Carlos III (RETICS-FEDER RD16/0008/0016), FARPE-FUNDALUCE, Generalitat Valenciana-FEDER (IDIFEDER/2017/064, PROMETEO/2021/024, APOSTD/2020/245), Es Retina Asturias (2019/00286/001), and Michael J Fox Foundation for Parkinson’s Research.
|© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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|INV - NEUROVIS - Artículos de Revistas
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