Abstract
Purpose :
Diverse studies have shown the existence of visual alterations in Parkinson disease, but how it affects different retinal cell types remains unknown. This study aims to characterize some of the cellular changes that occur in the retina of Parkinson disease donors. Concretely, we looked for the presence of phosphorylated α-synuclein, the impairment of the dopaminergic system and the loss of cells in the ganglion cell layer.
Methods :
Whole eyes were obtained postmortem from Parkinson disease (PD) and control healthy donors (C). Immunohistochemistry using the avidin-biotin-complex method or fluorescence labeling was performed. Flat wholemount retinas were stained using an antibody raised against α-synuclein phosphorylated at serine 129 (p-synuclein; N=10 PD, 12 C) and structures accumulating the protein were analyzed. A score based on the amount of staining was given to each retina and compared to its brain score using the Spearman correlation test. Antibodies against tyrosine hydroxylase (N=9 PD, 4 C) and calretinin (N=9 PD, 4 C) were also employed. Morphology, density and number of synaptic contacts of dopaminergic and AII amacrine cells were established. Cells in the ganglion cell layer were stained with Hoescht (N=4 PD, 4 C) and cell density was calculated. T-tests were used for statistical analysis.
Results :
P-synuclein staining was found in ganglion cells, axons, somas, dendrites and abnormal structures. The density of p-synuclein-immunoreactive structures present in the retina significantly correlated with that found in ten standard brain regions (R=0.849; p<0.001). A significant decrease of dopaminergic cell density was found in Parkinson disease (PD=10.43±2.04, C=18.64±1.06; p<0.001) while no differences were found in AII amacrine cell density. Synaptic contacts between dopaminergic and AII cells were also reduced. Finally, a significant loss of cells in the ganglion cell layer was detected (p<0.05).
Conclusions :
Accumulation of p-synuclein, impairment of the dopaminergic system and loss of cells in the ganglion cell layer may explain the visual alterations detected in Parkinson disease and could be employed as biomarkers of the presence or progression of the disease. These findings indicate that the retina may be a useful model with which to study the neurodegenerative mechanisms underlying Parkinson disease.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.