Experimental justification for the possibility of prediction of the development of neurodegenerative diseases following gamma-sinuclein dysfunction based on the influence of dopaminergic system on the intraocular pressure.

Abstract

Synucleins are a family of synaptic proteins involved in vesicular transport and release of neurotransmitters, particularly dopamine. Pathological aggregation of these proteins is associated with development of several neurodegenerative diseases (NDD), and gamma-synuclein was shown to be related with glaucoma. At present, there are no available diagnostic methods for identifying groups at risk of NDD or other diseases related with γ-synuclein dysfunction by the effect of adrenergic and dopaminergic regulators on intraocular pressure (IOP). A difficulty in developing such methods is that NDDs are diagnosed by clinical symptoms when the process is already practically irreversible. The aim of this study was experimental justification of a possibility for predicting the γ-synuclein dysfunction by the effect of adrenergic and dopaminergic regulators on IOP. Methods. A strain of knockout mice with inactivated gamma-synuclein gene (gamma-KO) was used for developing a method for detection of γ-synuclein dysfunction. The method included measurement of IOP before and after instillation of drugs regulating the dopaminergic system activity. Results. Gamma-KO mice showed a statistically significant decrease in IOP following the instillation of 0.1% Melatonin, 0.2% Haloperidol, or 10% Dopamine compared to the wild type control. Conclusion. The suggested method allows detecting and predicting the development of γ-synuclein dysfunction and its influence on the IOP regulation and, thus, to identify groups of risk to be monitored and preventively treated.