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Neurosci Lett. 2014 Jun 13;571:34-8. doi: 10.1016/j.neulet.2014.04.027. Epub 2014 Apr 28.

Phosphorylated α-synuclein-immunoreactive retinal neuronal elements in Parkinson's disease subjects.

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Banner Sun Health Research Institute, 10515W. Santa Fe Drive, Sun City, AZ 85351, United States. Electronic address:
Banner Sun Health Research Institute, 10515W. Santa Fe Drive, Sun City, AZ 85351, United States.
Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259, United States.
Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
Departamento de Fisiología, Genética y Microbiología, Universidad de Alicante, Spain.


Visual symptoms are relatively common in Parkinson's disease (PD) and optical coherence tomography has indicated possible retinal thinning. Accumulation of aggregated α-synuclein is thought to be a central pathogenic event in the PD brain but there have not as yet been reports of retinal synucleinopathy. Retinal wholemounts were prepared from subjects with a primary clinicopathological diagnosis of PD (N=9), dementia with Lewy bodies (DLB; N=3), Alzheimer's disease (N=3), progressive supranuclear palsy (N=2) as well as elderly normal control subjects (N=4). These were immunohistochemically stained with an antibody against α-synuclein phosphorylated at serine 129, which is a specific molecular marker of synucleinopathy. Phosphorylated α-synuclein-immunoreactive (p-syn IR) nerve fibers were present in 7/9 PD subjects and in 1/3 DLB subjects; these were sparsely distributed and superficially located near or at the inner retinal surface. The fibers were either long and straight or branching, often with multiple en-passant varicosities along their length. The straight fibers most often had an orientation that was radial with respect to the optic disk. Together, these features are suggestive of either retinopetal/centrifugal fibers or of ganglion cell axons. In one PD subject there were sparse p-syn IR neuronal cell bodies with dendritic morphology suggestive of G19 retinal ganglion cells or intrinsically photosensitive ganglion cells. There were no stained nerve fibers or other specific staining in any of the non-PD or non-DLB subjects. It is possible that at least some of the observed visual function impairments in PD subjects might be due to α-synucleinopathy.


Autopsy; Diagnosis; Ganglion cell; Lewy body; Melanopsin; Pathology

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