Tear Proteins as Possible Biomarkers for Parkinson’s Disease

Abstract

Purpose : Non-motor features of Parkinson's disease (PD) occur years before motor dysfunction. Lacrimal glands are highly innervated by cholinergic neurons, while tear fluid secreted by lacrimal glands is greatly stimulated by cholinergic neurons. The production, packaging and secretion of specific proteins into tears may be regulated by early changes in nerve function to lacrimal glands. Analysis of alterations in the secretion of proteins into tears may identify reliable and non-invasive biomarkers for PD at different stages of the disease. Our goal was to evaluate whether tear protein composition differs in individuals with PD versus people without PD.

Methods : Tear samples from 60 diagnosed PD patients of varying severity and 30 age- and gender-matched non-PD controls were collected utilizing an anesthetized Schirmer’s test, eluted, and pooled from both eyes for analysis. Alpha synuclein and matrix metallopeptidase 9 (MMP9) were measured using a human magnetic luminex assay kit (R&D systems) while lactoferrin (LF) was measured using a human lactoferrin ELISA kit (Abcam). Oligomeric alpha-synuclein was measured using a human alpha-synuclein oligo ELISA kit (My BioSource). Total protein concentration was measured using the Bio-Rad assay (Bio-Rad). Results are presented as mean ± SEM.

Results : Total alpha synuclein decreased significantly in PD patients (423.81 ± 50.7 pg/mg tear protein) relative to healthy controls (695.71 ± 125.8 pg/mg tear protein) (p-value=0.05) in tears from patients acquired from Schirmer’s strips taken during the anesthetized Schirmer’s test. However, oligomeric alpha synuclein increased significantly in PD patients (1.38 ± 0.29 ng/mg tear protein) relative to healthy controls (0.42 ± 0.16 ng/mg tear protein) (p-value= 0.005). While detectable in tears, neither MMP9 nor LF varied significantly between PD patients and controls. Total protein concentration was elevated significantly in PD patients (3.91 ± 0.23 mg/ml) relative to healthy controls (2.96 ± 0.22 mg/ml) (p-value=0.004).

Conclusions : Total alpha synuclein and oligomeric synuclein may have the potential to discriminate between tears of PD patients and healthy controls. To our knowledge this is the first report of tear collection and protein analysis as a possible non-invasive, relatively inexpensive and reliable biomarker for PD.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.