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

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Abstract
Parkinson’s disease (PD) diagnosis is currently made by clinical observation of motor symptoms when around 50% of dopamine neurons in the substantia nigra pars compacta are already lost. Non-motor symptoms, such as vision problems, occur earlier during disease progression and could be caused by altered retinal functioning. Various techniques exist to detect retinal alterations and, therefore, could provide biomarkers for earlier diagnosis of PD. The aim of this project is to determine potential retinal biomarkers for PD 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. 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. The post-illumination pupillary response showed a consistently larger pupil diameter post-MPTP. Post-mortem examination revealed a significant thinning of the outer nuclear retinal layer. Tyrosine hydroxylase and melanopsin-containing cells were reduced in MPTP-intoxicated monkeys. Altogether, these results indicate that MPTP intoxication leads to functional retinal changes detectable by ERG and pupillometry, possibly attributed to cellular alterations.
Funding Information
  • Mitacs (Mitacs accelerate #IT28655)
  • Natural Sciences and Engineering Research Council of Canada (NSERC #538422-18)
  • Canadian Institutes of Health Research (CIHR PJT 470155)
  • Canada Foundation for Innovation (CIF 42160)
  • Fonds de recherche du Québec (FRQ-S, 268922)

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