Improving Parkinson’s disease diagnosis by non-invasive detection of retinal biomarkers in MPTP monkeys using ERG and pupillometry

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Abstract
Diagnosis of Parkinson’s disease (PD) is currently made following clinical observation of motor symptoms. By the time these symptoms manifest, around 50% of dopamine neurons are lost in the substantia nigra pars compacta, limiting the possibility of implementing potential neuroprotective treatments that could delay the progression of the disease. Non-motor symptoms, such as vision problems, occur much earlier along the progression of the disease. If altered functioning of the retina causes these vision problems, various techniques could be implemented to detect retinal changes, therefore providing early biomarkers for PD. The aim of this project is to determine potential biomarkers for PD via the retina by using electroretinography (ERG) and pupillometry. In vivo measurements were performed on four non-human primates, before and after they were rendered parkinsonian by administration of 1-méthyl-4-phényl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that induces degeneration of dopamine neurons. Post-mortem retinal analyses were compared against the retina of four additional control monkeys. ERG results showed a significant increase in photopic b-wave implicit time and reduced oscillatory potential (OP) amplitudes in both photopic and scotopic conditions following MPTP administration. These OP amplitudes were restored following L-dopa administration. Analysis of the post-illumination pupillary response showed a consistently larger pupil diameter postMPTP. Post-mortem examination reveals a significant thinning of the outer nuclear retinal layer. A reduced number of tyrosine hydroxylase and melanopsin containing cells is also found in MPTP-intoxicated monkeys. Altogether, these results indicate that MPTP-induced degeneration of dopamine neurons leads to functional changes to the retina detectable by ERG and pupillometry, and that these changes could be attributed to cellular alterations in the retina as observed post-mortem. This study provides evidence for potential retinal biomarkers that could be used as an earlier or more accurate means of diagnosing PD.

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