Tear Fluid Catecholamines As Biomarkers of the Parkinson’s Disease: A Clinical and Experimental Study

Abstract

An important approach to an early diagnosis of Parkinsons disease (PD) is screening for peripheral biomarkers in patients at the early clinical stage. In this study, we evaluated catecholamine concentration changes in the tear fluid of untreated PD patients as biomarkers. Norepinephrine and dopamine concentrations in the tear fluid of patients were found to increase compared to those in age controls, which was especially pronounced on the side where motor symptoms appeared. On the contrary, the epinephrine concentration in the tear fluid of patients was reduced bilaterally. Since there was no reason to consider the markers found in the clinical stage of PD as markers of the preclinical stage, we additionally studied the tear fluid composition in mouse neurotoxic models of PD preclinical and clinical stages. The norepinephrine concentration in the tear fluid of mice from the clinical stage model was found to be higher than that in controls; in the preclinical stage model, the norepinephrine concentration had a tendency to increase. Therefore, both PD patients and mice from PD preclinical and clinical stage models manifest unidirectional changes in their tear fluid compositions, which may be considered as promising biomarkers for the development of early diagnosis.

Native fluorescence of tear fluid as a tool for diagnostics of glaucoma

“…epinephrine, norepinephrine, dopamine (all three located at l ex /Dl z 280/50 nm), or serotonin (l ex /Dl z 270/70 nm), 20 all present in tear uid. 21,22 These compounds altogether contribute to the shape and uorescence intensity of the main peak in the tear uid 3-D uorescence spectrum.…”

Molecular Mechanisms and Clinical Manifestations of Catecholamine Dysfunction in the Eye in Parkinson’s Disease As a Basis for Developing Early Diagnosis

“…Напротив, концентрация адреналина ОБЗОРЫ в слезной жидкости больных снижена с обеих сторон. Также у больных БП и у мышей на моделях доклинической (до развития двигательных симптомов) и ранней клинической стадий паркинсонизма выявлено повышение концентрации норадреналина в слезной жидкости [114]. Стоит отметить, что изменение содержания белка и катехоламинов в слезе при экспериментальном паркинсонизме, вероятно, связано с нарушением иннервации слезной железы на стадии до моторных нарушений.…”

“…On the contrary, the adrenaline concentration in patients’ lacrimal fluid was evenly reduced both on the ipsilateral and contralateral sides. Furthermore, the norepinephrine concentration in the lacrimal fluid was increased in patients with PD and in mice, in models of preclinical (before the motor symptoms emerged) and early clinical stages of Parkinsonism [ 114 ]. It is worth noting that changes in the levels of the protein and catecholamines in the tear fluid in experimental Parkinsonism are probably related to impaired innervation of the lacrimal gland at the stage before mobility impairments develop.…”

Biofluid Markers for Prodromal Parkinson's Disease: Evidence From a Catecholaminergic Perspective

“…Goldstein et al ( 45 ) also clinically evaluated 26 prodromal subjects who had at least three risk factors for PD, i.e., olfactory dysfunction, RBD, OH, and/or genetic predisposition, and, no motor symptoms. Finally, Kim et al ( 46 ) assessed tear fluid catecholamines in 26 untreated dnPD patients having Hoehn and Yahr stages I–II.…”

“…At first glance, (i) three CSF and plasma metabolites [DOPAC ( 41 , 43 , 45 ), DHPG ( 41 , 42 ), l -DOPA ( 41 , 43 , 45 )], (ii) one plasma and three tear fluid catecholamines [N(A) ( 40 , 41 , 46 ), DA ( 46 )], and (iii) two derivative plasma trace amines [tyramine ( 47 ) and octopamine ( 40 ), whether or not combined with plasma NA ( 47 )] seem promising as markers for prodromal or dnPD ( Table 1 ). Regarding CSF DOPAC, results are quite unequivocal, with very low to low levels across PD stages, from prodromal ( 45 ) to de novo ( 41 ) and early-stage ( 43 ).…”