Lacrimal glands are highly innervated by cholinergic and other neurons, and tear fluid secreted by lacrimal glands is greatly stimulated by parasympathetic and sympathetic neural pathways.  The production, packaging and secretion of specific proteins into tears may change in response to alterations in nerve function to lacrimal glands and cornea, which may be tested by collection of reflex tears.   Reflex tears are stimulated tears collected with an unanesthetized Schirmer’s test. We have previously reported results with basal tears/anesthetized Schirmer’s test.

To evaluate whether the protein composition of reflex tears differs in individuals with Parkinson’s disease (PD) versus Healthy Controls (HC)

Oligomeric alpha-synuclein was significantly increased by 4.7-fold in PD tears (4.21 ± 0.50 ng/mg tear protein) relative to HC (0.90 ± 0.13 ng/mg tear protein) (p<0.0001, AUROC=0.8).  CCL2 showed a significant increase in PD tears at 165.8 ± 17.2 pg/mg tear protein (p=0.05, AUROC=0.65) relative to HC at 116.3 ± 18.4 pg/mg tear protein.  In male PD patients, greater changes relative to male HC were noted for oligomeric alpha synuclein (4.95 ± 0.71 ng/mg tear protein in PD relative to 0.89 ± 0.18 ng/mg tear protein in HC, p<0.0001, AUROC=0.83)  and CCL2 (201.5 ± 26.7 pg/mg tear protein relative to 117.9 ± 29.6 pg/mg tear protein, p=0.0004, AUROC=0.72), relative to that seen in female PD versus female HC. 

Oligomeric synuclein levels enable discrimination between reflex tears of PD patients and HC. CCL-2 may represent an additional biomarker.  The origin of sex differences in biomarker values requires further study.