Starburst amacrine cells,involved in visual motion perception,lose their synaptic input from dopaminergic amacrine cells and degenerate in Parkinson’s disease patients  

作　　者：Xavier Sánchez-Sáez Isabel Ortuño-Lizarán Carla Sánchez-Castillo Pedro Lax Nicolás Cuenca 

机构地区：[1]Department of Physiology,Genetics and Microbiology,University of Alicante,San Vicente del Raspeig,Spain [2]Alicante Institute for Health and Biomedi-cal Research(ISABIAL),Alicante,Spain [3]Ramón Margalef Institute,University of Alicante,San Vicente del Raspeig,Spain.

出　　处：《Translational Neurodegeneration》2023年第1期638-653,共16页转化神经变性病（英文）

基　　金：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);Michael J Fox Foundation for Parkinson’s Research.

摘　　要：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.

关 键 词：Parkinson’s disease Retinal neurodegeneration Human retina ChAT amacrine cells Dopaminergic amacrine cells 

分 类 号：R742.5[医药卫生—神经病学与精神病学]