Tränenflüssigkeit als mögliche Quelle für Biomarker bei Patienten mit einem idiopathischem Parkinson-Syndrom

Idiopathic Parkinson's disease is the second most common neurodegenerative disorder worldwide with a growing prevalence in the continuously aging population. Until today, the diagnosis of Parkinson's disease is mainly based on the evaluation of distinctive clinical features and the differentiation from atypical parkinsonian syndromes and Parkinson's disease mimics. Despite remarkable developments in the field of diagnostics, the evaluation of Parkinson's disease patients can be challenging, particularly in oligosymptomatic early stages when distinctive clinical features are not that obvious. Therefore, biomarkers could contribute to an improved diagnostic accuracy. Tear fluid is an easily accessible body fluid reflecting pathophysiological changes in systemic and ocular diseases and is already used as a biomarker source for several ophthalmological disorders. Here, we analyzed the tear fluid of patients with Parkinson's disease and age-matched controls to describe disease-related changes in tear fluid and identify putative biomarkers for the diagnosis of Parkinson's disease. Therefore, unstimulated tear fluid samples of a pilot cohort with 36 Parkinson's disease patients and 18 controls were collected via Schirmer tear test strips and then analyzed via a Bottom-up liquid chromatography electrospray ionization tandem mass spectrometry workflow, followed by functional analysis encompassing protein-protein interaction as well as cellular component and pathway analysis. This mass spectrometric analysis lead to the identification of 571 tear proteins, whereby 31 proteins were exclusively detected in the Parkinson's disease group and 7 only in the control group. Whereas 21 proteins were significantly increased in the Parkinson's disease versus control group, 19 proteins were significantly decreased. Core networks of proteins involved in immune response, lipid metabolism and oxidative stress were distinctly altered in Parkinson's disease patients. Several proteins that are already well known in neurodegenerative disorders were identified. To our best knowledge, this is the first description of tear fluid proteome in Parkinson's disease patients. Tear protein level alterations suggest the contribution of different disease-related mechanisms in ocular pathology in Parkinson's disease and propose candidate proteins to be validated as potential biomarkers in larger cohorts.2022-03-3