Development of differential and early (preclinical) diagnostics of Parkinson’s disease (PD) is among the priorities in neuroscience. We searched for changes in the level of catecholamines and α-2-macroglobulin activity in the tear fluid (TF) in PD patients at an early clinical stage. It was shown that TF in patients is characterized by an increased level of noradrenaline mainly on the ipsilateral side of pronounced motor symptoms (72%, p = 0.049), a decreased level of adrenaline on both sides (ipsilateral—53%, p = 0.004; contralateral—42%, p = 0.02), and an increased α-2-macroglobulin activity on both sides (ipsilateral—53%, p = 0.03; contralateral—56%, p = 0.037) compared to controls. These changes are considered as potential biomarkers for differential diagnosis. Similar changes in the TF were found in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice when modeling clinical and preclinical stages of PD. These data show the adequacy of models to the pathogenesis of PD along the selected metabolic pathways, and also suggest that the found TF changes can be considered as potential biomarkers for preclinical diagnosis of PD. In Parkinsonian mice, the level of catecholamines also changes in the lacrimal glands, which makes it possible to consider them as one of the sources of catecholamines in the TF.

This review provides information onthe non-motor peripheral manifestations of Parkinsons disease (PD) associated with a pathology of the visual analyzer and the auxiliary apparatus of the eye. The relationship between neurodegenerative processes that take place in the brain and in the eye opens new prospects to use preventive ophthalmologic examination todiagnose PD long before the characteristic motor symptoms appear. This will encourage the use of neuroprotective therapy, which stops, or at least slows down, neuronal death, instead of the current replacement therapy with dopamine agonists. Animportant result of an eye examination of patients with PD may be a non-invasive identification of new peripheral biomarkers manifesting themselvesas changes in the composition of the lacrimal fluid.

Dysregulation of intraocular pressure (IOP) is one of the main risk factors for glaucoma. γ-synuclein is a member of the synuclein family of widely expressed synaptic proteins within the central nervous system that are implicated in certain types of neurodegeneration. γ-synuclein expression and localization changes in the retina and optic nerve of patients with glaucoma. However, the mechanisms by which γ-synuclein could contribute to glaucoma are poorly understood. We assessed the presence of autoantibodies to γ-synuclein in the blood serum of patients with primary open-angle glaucoma (POAG) by immunoblotting. A positive reaction was detected for five out of 25 patients (20%) with POAG. Autoantibodies to γ-synuclein were not detected in a group of patients without glaucoma. We studied the dynamics of IOP in response to IOP regulators in knockout mice (γ-KO) to understand a possible link between γ-synuclein dysfunction and glaucoma-related pathophysiological changes. The most prominent decrease of IOP in γ-KO mice was observed after the instillation of 1% phenylephrine and 10% dopamine. The total protein concentration in tear fluid of γ-KO mice was approximately two times higher than that of wild-type mice, and the activity of neurodegeneration-linked protein α2-macroglobulin was reduced. Therefore, γ-synuclein dysfunction contributes to pathological processes in glaucoma, including dysregulation of IOP.

Purpose: to investigate the changes of electrophysiological activity of healthy rabbit retina occurring in courses of fractal stimulation (FS) of varied duration in order to obtain new scientific data on how fractal visual signals of low intensity, self-similar with respect to time, affect the retina.Material and methods. 12 healthy Chinchilla rabbits (24 eyes), were examined before and after FS courses that lasted 1, 4 or 12 weeks, using electroretinographic (ERG), morphometric (optical coherence tomography) and biochemical methods (detection of dopamine in the tear). For FS of rabbits, a device with an LED emitter was developed, which generates nonlinear brightness fluctuation based on the Weierstrass — Mandelbrot fractal functions. The choice of fractal signal parameters used in the work was substantiated. Pattern ERG and ganzfeld ERG were registered according to ISCEV standards; also, photopic flicker ERG was recorded at 8.3, 10, 12, and 24 Hz.Results. No negative effects of a 12-month FS course on the activity and morphology of the retina, or on dopaminergic processes in the eye of a healthy animal were found, which confirms the safety of using low-intensity FS in the clinic. A statistically significant increase in the amplitude of low-frequency flicker ERGs, a shortening of peak latency, and an increase in the amplitude of the b-wave of the scotopic and photopic ERGs was noted.Conclusion. To assess possible therapeutic effects of FS, we need to continue the investigation on animal models and human patients with retinal pathology. Considering the changes of retinal activity as revealed in the present paper, we recommend the duration of FS courses from 1 week to 1 month for future studies.

Purpose: to prepare and characterize calcium-phosphate nanoparticles loaded with compounds of different nature: low-molecular inhibitor of angiotensin-converting enzyme lisinopril, and high-molecular enzyme superoxide dismutase 1. To estimate the possibility of enhancing the biological efficacy of these compounds via incorporation to the nanoparticles.Material and methods. To increase the stability of calcium-phosphate nanoparticles coating with β-D-cellobiose was used. The size, surface charge (ζ-potential) of the particles and efficacy of including of the selected compounds to the particles were measured. Comparative assessment of the efficacy of lisinopril solution and lisinopril in nanoparticles was made via the estimation of their ocular hypotensive effect in normotensive rabbits. To compare the efficacy of the superoxide dismutase 1 solution and superoxide dismutase 1 in nanoparticles the rabbit model of immunogenic uveitis was used. We estimated the clinical score for several signs of uveitis, protein level, and antioxidant activity in aqueous humor.Results. Calcium-phosphate nanoparticles containing lisinopril had average hydrodynamic radius of 170–300 nm and negative ζ-potential of –17 mV. Particles containing superoxide dismutase 1 had average hydrodynamic radius of 220–450 nm and negative ζ-potential of –4 mV. Lisinopril in nanoparticles caused a significantly greater decrease of intraocular pressure than lisinopril solution. Superoxide dismutase 1 in calcium-phosphate nanoparticles more efficiently decreased the clinical manifestations of uveitis and normalized the biochemical processes in aqueous humor than the enzyme in buffer solution.Conclusion. Incorporation of both low-molecular and high-molecular drugs to the calcium-phosphate nanoparticles enhance their bioavailability and therapeutic efficiency. The data obtained give evidence of the prospectively of the using of these nanoparticles as vehicles for the ophthalmic drugs used in eyedrops.

Diabetic retinopathy (DR) is becoming more and more widespread disease. Investigation of local changes of metabolic pathways in the eye improves our knowledge about diabetic retinopathy pathogenesis and provide perspective for the development of new pathogenetically based and individually focused therapy of this disease.Purpose of the study was to determine the concentrations of angiotensin II (AII), angiotensin-converting enzyme (ACE) and matrix metalloprotease-9 (MMP-9) in tears and serum of patients with diabetic retinopathy, estimate their significance for the evaluation of diabetic retinopathy severity and choice of treatment.Patients and methods. Tear and serum samples from 31 patients with diabetic retinopathy were analysed. Control group consisted of healthy volunteers of the same sex and age. Concentrations of angiotensin II, angiotensin-converting enzyme and matrix metalloprotease-9 were measured using the ELISA kits.Results: in controls angiotensin II concentration was 9.8 ± 5.5 pg/ml, in tears — 11.8 ± 6.6 pg/ml, angiotensin-converting enzyme concentration in serum was 82.6 ± 10.9 ng/ml, in tears it was 40 times lower: 2.5 ± 0.5 ng/ml, matrix metalloprotease-9 concentration in serum was 186.3 ± 8.9 ng/ml while in tears it was 100 times lower: 2.0 ± 0.9 ng/ml. In tears of patients with diabetic retinopathy levels of all 3 substances were significantly higher than in controls. Concentration of angiotensin II was 8 times higher, angiotensin-converting enzyme concentration 5 times higher and matrix metalloprotease-9 level 3 times higher. In serum angiotensin II concentration was increased 9 times, angiotensin-converting enzyme — 2 times. No difference in serum matrix metalloprotease-9 levels was observed. Thus diabetic retinopathy cause a significant activation of local and systemic rennin-angiotensin system. Local changes are more marked than systemic. Estimation of angiotensin II, angiotensin-converting enzyme and matrix metalloprotease-9 concentrations in tears can serve as an objective test for the diabetic retinopathy diagnostic and a pathogenetic rationale for the development of a new method of therapy — topical use of angiotensin-converting enzyme inhibitors.