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.

Authors

  • T.A. Pavlenko Helmholtz National Medical Research Center of Eye Diseases, Sadovaya-Chernogryazskaya Str. 14/19, Moscow 105062, Russia. https://orcid.org/0000-0001-8032-4248
  • M.S. Kukharsky Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severny Proezd 1, Chernogolovka 142432, Russia; N.I. Pirogov Russian National Research Medical University, Ostrovityanova Str. 1, Moscow 117997, Russia https://orcid.org/0000-0001-5080-2544
  • A.V. Grigoryev Helmholtz National Medical Research Center of Eye Diseases, Sadovaya-Chernogryazskaya Str. 14/19, Moscow 105062, Russia
  • S.V. Struchkova Helmholtz National Medical Research Center of Eye Diseases, Sadovaya-Chernogryazskaya Str. 14/19, Moscow 105062, Russia http://orcid.org/0000-0003-4480-1953
  • O.V. Beznos Helmholtz National Medical Research Center of Eye Diseases, Sadovaya-Chernogryazskaya Str. 14/19, Moscow 105062, Russia https://orcid.org/0000-0001-7557-4955
  • N.B. Chesnokova Helmholtz National Medical Research Center of Eye Diseases, Sadovaya-Chernogryazskaya Str. 14/19, Moscow 105062, Russia https://orcid.org/0000-0002-7856-8005

DOI:

https://doi.org/10.25557/0031-2991.2020.04.5-11

Keywords:

neurodegenerative diseases, gamma-syinucleinopathy, intraocular pressure, dopaminergic system regulators, knock-out mice.

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.

Author Biographies

  • T.A. Pavlenko, Helmholtz National Medical Research Center of Eye Diseases, Sadovaya-Chernogryazskaya Str. 14/19, Moscow 105062, Russia.
    канд. мед. наук, ст. науч. сотр. отдела патофизиологии и биохимии ФГБУ «НМИЦ ГБ им. Гельмгольца» Минздрава России
  • M.S. Kukharsky, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severny Proezd 1, Chernogolovka 142432, Russia; N.I. Pirogov Russian National Research Medical University, Ostrovityanova Str. 1, Moscow 117997, Russia
    https://orcid.org/0000-0001-5080-2544
  • A.V. Grigoryev, Helmholtz National Medical Research Center of Eye Diseases, Sadovaya-Chernogryazskaya Str. 14/19, Moscow 105062, Russia
    канд. мед. наук, зав. клин. лаб. диагн. отдела патофизиологии и биохимии ФГБУ «НМИЦ ГБ им. Гельмгольца» Минздрава России
  • S.V. Struchkova, Helmholtz National Medical Research Center of Eye Diseases, Sadovaya-Chernogryazskaya Str. 14/19, Moscow 105062, Russia
    .
  • O.V. Beznos, Helmholtz National Medical Research Center of Eye Diseases, Sadovaya-Chernogryazskaya Str. 14/19, Moscow 105062, Russia
    .
  • N.B. Chesnokova, Helmholtz National Medical Research Center of Eye Diseases, Sadovaya-Chernogryazskaya Str. 14/19, Moscow 105062, Russia
    .

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Published

2020-11-26

Issue

Section

Original research

How to Cite

[1]
2020. 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. Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya (Pathological physiology and experimental therapy). 64, 4 (Nov. 2020), 5–11. DOI:https://doi.org/10.25557/0031-2991.2020.04.5-11.