Early detection of Parkinson's disease: Retinal functional impairments as potential biomarkers

Abstract

Background: Parkinson's disease is typically diagnosed after substantial neurodegeneration despite early non-motor symptoms manifesting decades earlier. These changes offer a promising avenue for diagnostic exploration, especially within the eye, which has been proposed as a "window to the brain."

Objective: The aim was to identify biomarkers by validating the use of electroretinography, a non-invasive technique, to detect early retinal function anomalies reflecting central dysfunction.

Methods: Homozygous M83 transgenic mice (n = 10 males, 11 females), overexpressing human A53T α-synuclein, underwent behavioral tests and electroretinography measurements. Histological evaluation was performed at four months to analyze synucleinopathies and neurodegeneration. Electroretinography was also conducted with idiopathic PD patients (mean age 63.35 ± 7.73; disease duration 4.15 ± 2.06; H&Y score 2.07 ± 0.59; n = 12 males, 8 females) and healthy age-matched controls (mean age 61.65 ± 8.39; n = 9 males, 11 females).

Results: Rodent electroretinography revealed reduced photopic b-wave, PhNR b-wave, and PhNR-wave amplitudes at two and four months, particularly in females, indicating bipolar and retinal ganglion cell impairment. Based on retinal histological assessment, these changes might arise from α-synuclein pathology occurring in outer retinal layers. Likewise, the scotopic b-wave and PhNR waveform were similarly impaired in female participants with Parkinson's disease. The scotopic oscillatory potentials isolated further identified an attenuated amacrine cell output in females.

Conclusions: Findings from both mice and human cohorts indicate that retinal functional impairments can be detected early in the progression of Parkinson's disease, particularly among females. These tools show promise in facilitating early diagnosis, disease monitoring, therapeutic intervention, and ultimately enhancing patient outcomes.

Keywords: Biomarkers; Diagnosis; Electroretinography; Parkinson's; Retina.