Impairment of amacrine starburst cells and their synaptic contacts with dopaminergic cells could explain motion perception disturbances in Parkinson's disease

Abstract

AbstractPurpose: Parkinson's disease (PD) patients suffer from visual deficiencies in the early stages of the disease. One of these visual symptoms is the impairment of the motion perception. In that sense, we wanted to determine if the starburst amacrine cells (the main cell type involved in motion perception) are degenerated in PD. Also, we sought to evaluate if this possible degeneration is related to the degeneration of the dopaminergic system.Methods: Post‐mortem human eyes from control and PD donors were used in this study. Immunohistochemistry and confocal microscopy were used in whole‐mount retinas to evaluate tyrosine hydroxylase‐positive cell density (dopaminergic amacrine cells), and choline acetyltransferase‐positive cell density (starburst amacrine cell). Moreover, we quantified the dopaminergic synaptic contacts with starburst amacrine cells using vesicular monoamine transporter‐2 (VMAT2) antibodies.Results: There is a decrease in the dopaminergic amacrine cell density in PD retinas. Furthermore, we found a decrease in the number of starburst amacrine cells. Importantly, we describe for the first time that dopaminergic amacrine cells contact with starburst amacrine cells in the retina and that these connections decrease in PD patients.Conclusions: This work shows the degeneration of starburst amacrine cells and their synaptic connections with dopaminergic cells, and this may explain the disturbances in motion perception present in PD. Importantly, these deficiencies can be used as a biomarker of this pathology performing functional tests for visual motion perception.Support: Ministerio de Ciencia e Innovación (FEDER‐ PID2019‐106230RB‐I00). Ministerio de Universidades (FPU16/04114). Instituto Carlos III (RETICS‐FEDER RD16/0008/0016). Generalitat Valenciana (IDIFEDER/2017/064, ACIF/2020/203). Michael J Fox Foundation for Parkinson's Research.