An Exploratory Analysis of Differential Tear Fluid miRNAs in Patients with Parkinson’s Disease and Atypical Parkinsonian Syndromes

Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) are neurodegenerative disorders diagnosed by clinical criteria with limited diagnostic specificity in early stages. Diagnostic biomarkers facilitating early and precise diagnosis are needed. Tear fluid (TF) is an easily accessible body fluid reflecting pathophysiological changes in ocular and systemic diseases. In this exploratory study, we investigate TF as a non-invasive source of disease-specific miRNAs for PD, MSA, and PSP. We demonstrate reduced TF production in PD patients. Using a real-time quantitative PCR-based array targeting 1113 miRNAs, we identified 55 exclusively expressed in PD, 35 in PSP, and 14 in MSA, respectively. Several of these have previously been identified in other biofluids. Overrepresentation analysis of target genes showed apoptotic and cell differentiation pathways as common targets. While these findings suggest that miRNA alterations in TF might reflect disease mechanisms in PD and atypical Parkinsonian syndromes, the exploratory character of the study combined with the use of pooled samples, indicates the need for further validation. The small sample size highlights the importance of follow-up studies with larger, more definitive cohorts to confirm the potential of these miRNAs as reliable biomarkers.