Literature Review

Retinal Changes Indicate Parkinson’s Disease Pathology Severity

Lewy-type synucleinopathy density in the retina significantly correlates with that in the brain.


 

The accumulation of phosphorylated α-synuclein in the retina may serve as a biomarker of brain pathology severity and aid in diagnosis and monitoring of Parkinson’s disease, according to data published online ahead of print May 8 in Movement Disorders.

“These data suggest that phosphorylated α-synuclein accumulates in the retina in parallel with that in the brain, including in early stages preceding development of clinical signs of parkinsonism or dementia,” said Nicolás Cuenca, PhD, Assistant Professor of Physiology, Genetics, and Microbiology at the University of Alicante in Spain, and colleagues.

“The findings of this research invite the development of future applications leading to the utilization of retinal Lewy-type α-synucleinopathy as a Parkinson’s disease biomarker.”

Parkinson’s disease pathology is mainly characterized by the accumulation of pathologic α-synuclein deposits in the brain, but little is known about how synucleinopathy affects the retina.

Dr. Cuenca and colleagues used immunohistochemistry to evaluate the presence of phosphorylated α-synuclein deposits in the retina of nine autopsied subjects with Parkinson’s disease, four with incidental Lewy body disease, and six controls. Eligible subjects had motor parkinsonism, Lewy body pathology, and pigmented neuron loss in the substantia nigra at autopsy. For each subject, the researchers compared the amount of retinal synucleinopathy with indicators of brain disease severity.

All subjects with Parkinson’s disease and three subjects with incidental Lewy body disease had phosphorylated α-synuclein deposits in ganglion cell perikarya, dendrites, and axons. Some of the deposits resembled brain Lewy bodies and Lewy neurites. Cells that contained phosphorylated α-synuclein had different morphologies, soma sizes (ie, from 15 mm to 30 mm), dendritic lengths (ie, from 570 mm to 1,620 mm), and receptive fields. Control subjects did not show any phosphorylated α-synuclein immunoreactivity in their retina, however.

The Lewy-type synucleinopathy density in the retina significantly correlated with Lewy-type synucleinopathy density in the brain, with the Unified Parkinson’s disease pathology stage, and with the motor subscale of the Unifed Parkinson’s Disease Rating Scale. Confirmation of disease by autopsy partly compensated for the small number of subjects, according to the authors.

“This study is the first to demonstrate phosphorylated α-synuclein immunoreactive retinal structures similar to brain Lewy bodies and neurites,” said the researchers. “Further investigations of the eye in Parkinson’s disease are desirable, given that ocular structures are involved in the pathology of several neurodegenerative diseases.”

—Erica Tricarico

Suggested Reading

Ortuño-Lizarán I, Beach TG, Serrano GE, et al. Phosphorylated α-synuclein in the retina is a biomarker of Parkinson’s disease pathology severity. Mov Disord. 2018 May 8 [Epub ahead of print].

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