Tear biomarkers for Parkinson’s disease in basal versus reflex tears

Abstract

Purpose : PD patients often present with non-motor features and symptoms of cholinergic dysfunction years prior to motor symptoms. Tear secretion from the lacrimal gland is greatly stimulated by cholinergic neurons, thus the production, packaging and secretion of specific proteins into tears may be altered by changes in the function of nerves regulating lacrimal secretion. Tear proteins are a potential source of non-invasive biomarkers for PD at different stages of the disease. In this study, we evaluate whether the protein composition of basal and reflex tears differs in individuals with Parkinson’s disease (PD) versus healthy control (HC) individuals.

Methods : Basal tears from 93 PD patients of varying disease severity and 82 age- and gender-matched HC were collected with an anesthetized Schirmer’s test. Reflex tears were collected from 84 PD patients and 83 HC with an unanesthetized Schirmer’s test. Samples were pooled from both eyes for analysis of total α-synuclein (α-Syn_total), oligomeric α-synuclein (α-Syn_oligo), lactoferrin (LF) and Matrix Metallopeptidase 9 (MMP-9) by ELISA or multiplex ELISA, and values expressed as mean±SE

Results : α-Syn_total was significantly decreased in basal tears in PD patients (401.7±42.2 pg/mg tear protein) relative to HC (559.4±63.4 pg/mg tear protein) (p=0.0043, AUC ROC=0.63).
α-Syn_oligo was significantly increased in basal tears (3.46±0.59 ng/mg tear protein) relative to HC (0.92±0.15 ng/mg tear protein) (p<0.0001, AUC ROC=0.7). There was no difference in either LF or MMP-9 between PD patients and HC in basal tears. However, when measured in reflex tears, α-Syn_oligo was significantly increased in PD patients (4.30±0.50 ng/mg tear protein) relative to HC (0.89±0.13 ng/mg tear protein) (p<0.0001, AUC ROC=0.8) but α-Syn_total was unchanged. In reflex tears, a significant difference emerged in LF content in PD patients (326.21±53.2 µg/mg tear protein) vs HC (176.41±16.94 µg/mg tear protein)(p=0.002) but not in MMP-9.

Conclusions : Tear levels of α-Syn_oligo may have potential to discriminate between PD patients and HC. Reflex tear α-syn_oligo levels demonstrate a greater fold increase and sensitivity in distinguishing PD patients from HC than basal tears, and further show differences in LF that are not seen in basal tears, possibly due to increased engagement of the cholinergic pathway. Reflex tears may thus offer a more reliable and sensitive source of biomarkers for PD.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.