[The role of mitochondrial dysfunction in the stabilization of the glaucomatous process]. / Znachenie mitokhondrial'noi disfunktsii v stabilizatsii glaukomnogo protsessa.

Many key aspects of retinal ganglion cell (RGC) neurodegeneration in glaucoma are associated with mitochondrial dysfunction. Understanding the mechanisms and relationships between structural and functional changes in mitochondria would be beneficial for developing mitochondria-targeted therapeutic strategies to protect RGCs from glaucomatous neurodegeneration. PURPOSE: This study determines the extent of mitochondrial dysfunction in patients with primary open-angle glaucoma (POAG) and evaluates the potential for stabilizing the glaucomatous process by improving mitochondrial functional activity and energy production by therapy with Mexidol and Mexidol FORTE 250. MATERIAL AND METHODS: The study included 80 patients with moderate POAG with compensated intraocular pressure and 20 healthy volunteers. The extent of mitochondrial dysfunction was assessed by measuring the activity levels of mitochondrial enzymes: succinate dehydrogenase (SDH) and α-glycerophosphate dehydrogenase (α-GPDH) in peripheral blood lymphocytes using cytochemical analysis and cytometric morphology and density analysis (cytomorphodensitometry). Patients in the main group received sequential therapy with Mexidol as follows: Mexidol solution for intravenous and intramuscular administration at 50 mg/ml, 300 mg daily intramuscularly for 14 days, followed by Mexidol FORTE 250 tablets, one tablet three times daily for 56 days. Stabilization of glaucomatous optic neuropathy during treatment was evaluated using a comprehensive set of perimetric, electrophysiological, and structural-topographical methods at 14, 56, and 90 days. RESULTS: Sequential therapy in the main group resulted in a significant increase in mitochondrial enzyme activity at 14 and 56 days compared to baseline, with a gradual regression by the end of the observation period (90 days). This was accompanied by an increase in the number of mitochondria and an increase in their optical density as measured by cytomorphodensitometry. The improvement in mitochondrial enzyme activity at 14 and 56 days was associated with positive changes in the structural and functional parameters of the retina, as evidenced by static perimetry, optical coherence tomography, and a series of electrophysiological tests. CONCLUSION: The obtained data can be used to optimize POAG therapy by reducing mitochondrial dysfunction and stabilizing glaucomatous optic neuropathy.

[The effect of antioxidant therapy on some pathogenetic factors of primary open-angle glaucoma]. / Vliyanie antioksidantnoi terapii na nekotorye patogeneticheskie faktory pervichnoi otkrytougol'noi glaukomy.

In patients with glaucoma, one of the main initiating mechanisms that triggers the chain of events is disruption of the universal mechanism for regulating vascular tone due to endothelial dysfunction (ED). The main manifestation of ED is an imbalance of vasoconstrictor and vasodilator endothelial mediators, which inconsistency triggers the mechanisms of adaptive distress leading to the progression of morphological destruction, dyslipidemia, acceleration of atherogenesis, development of hemodynamic and hydrodynamic disorders. The drug Mexidol has a wide range of pharmacological activity and affects the main pathogenetic links of primary open-angle glaucoma (POAG). PURPOSE: The study analyzes the vascular remodulation, antioxidant and antihypoxic effects of the drug Mexidol in patients with PAOG. MATERIAL AND METHODS: The study included 78 patients with POAG of the early (n=43) and advanced stage (n=35) with average age of 67.8±1.5 years. The main study group consisted of 47 patients who received Mexidol in addition to local hypotensive treatment; 31 patients comprised the control group. In the comparison groups, the degree of ED was determined by the results of reactive hyperemia test, patients' blood plasma was analyzed for levels of stable nitric oxide metabolite (nitrite NO2-) and endothelin-1 (ET-1). General assessment of oxidative stress was carried out by high-performance liquid chromatography. Functional activity of the retina was studied using an electroretinograph and static computer perimetry performed according to the standard technique. RESULTS: The following changes are observed in patients of the main group using Mexidol: the index of oscillatory potentials significantly increases, peak latency decreases, perimeter indices show positive trends, vascular endothelial function improves according to reactive hyperemia test, concentration of vasoconstrictor mediator ET-1 in blood plasma decreases and of nitrite (NO2-) increases moderately, the coefficient of bioeffective vasotonic activity decreases, the level of glutathione peroxidase increases (p<0.05 compared to the baseline value), the level of malonyldialdehyde decreases, lipid metabolism improves (reduction in total cholesterol, low-density lipoprotein-cholesterol, triglycerides, decrease in the Atherogenic Index compared to the initial level). CONCLUSIONS: The drug Mexidol proved to be an effective endothelial protector, a powerful antioxidant and antihypoxant, contributed to deceleration of atherogenesis in patients with POAG.

[Therapeutic possibilities of stimulating reparative neurogenesis in patients with glaucoma who have recovered from a coronavirus infection]. / Terapevticheskie vozmozhnosti stimulyatsii reparativnogo neirogeneza u patsientov s glaukomoi, perenesshikh koronavirusnuyu infektsiyu.

In patients with glaucoma, the neuroplasticity of retinal cells, their axons and neuroglial elements is pathogenetically reduced, including due to a decrease in the concentration of neurotrophic factors. Coronavirus infections contribute to the damage processes, causing apoptosis of retinal and optic nerve cells. In this regard, the possibility of pharmacological stimulation of the production of these peptides through energy potentiation of the cell mitochondria function, reduction of oxidative stress severity and activation of interneuronal transduction system becomes relevant. PURPOSE: This study aimed to conduct a comprehensive diagnosis of the severity of oxidative stress, identify changes in the neuroplasticity and reparative ability of the retina in patients with primary open-angle glaucoma (POAG) who have recovered after a coronavirus infection, and are undergoing therapy with the complex drug Cytoflavin. MATERIAL AND METHODS: The study included 40 patients (mean age 57.2±3.6 years) with advanced POAG compensated by hypotensive agents; all of them recovered from moderate Covid-19 30 to 90 days prior to inclusion in the study. Twenty patients of the main group received therapy with the complex drug Cytoflavin, 20 other patients comprised the control group. In the comparison groups, the concentration of BDNF and CNTF in blood serum (SC) was determined by enzyme-linked immunosorbent assay (ELISA). Overall assessment of oxidative stress was done by high performance liquid chromatography. Studies of the functional activity of the retina were performed using the Tomey EP 1000 electroretinograph according to the standard method. RESULTS AND DISCUSSION: Retinal photosensitivity significantly improved in patients of the main group taking the complex drug Cytoflavin (mD mean after treatment increased from -7.34±0.62 dB to -4.52±0.12 dB (p>0.001), PSD mean decreased from 6.23±0.21dB to 4.27±0.13 dB (p>0.001)); the neural activity of the retina improved according to PERG (the amplitudes of the P50 and N95 components increased from 0.92±0.04 µv to 1.65±0.01 µv and from 1.83±0.06 µv to 2.68±0.01 µv, respectively (p>0.001), the latency of the P50 and N95 components decreased from 53.40±2.51 ms to 49.37±2.22 ms and from 112.40±5.23 ms to 107.4±8.11ms, respectively (p>0.001); the concentration of BDNF increased (from 18.65±5.32 ng/ml to 20.23±4.05 ng/ml (p>0.001)) and the concentration of CNTF in the blood serum decreased (from 3.99±0.37 pg/ml to 1.85±0.02pg/ml (p>0.001)), the severity of oxidative stress decreased (the indicator of oxidative stress decreased by 1.4 times after treatment p>0.001) and the content of antioxidant protection indicators increased: the indicator of antioxidant protection of blood serum increased by 1.4 times, the concentration of superoxide dismutase - by 1.9 times (p>0.001), glutathione peroxidase - by 1.4 times (p>0.001), coenzyme Q10 - by 4.5 times (p>0.001). CONCLUSION: The obtained data can be used to determine the risk of progression of glaucomatous optic neuropathy in patients with glaucoma who have had a coronavirus infection.

[Enzymatic activity of paraoxonase depending on polymorphism Q192R of the PON1 gene in patients with primary open-angle glaucoma]. / Fermentativnaya aktivnost' paraoksonazy v zavisimosti ot polimorfizma Q192R gena PON1 u patsientov s pervichnoi otkrytougol'noi glaukomoi.

It is believed that one of the main blood enzymes that hydrolyzes oxidized lipids incorporated in lipoproteins is the calcium-dependent hydrolase of paraoxonase 1, which has a significant antioxidant effect depending on the polymorphism of the PON1 gene. PURPOSE: To genotype patients with primary open-angle glaucoma (POAG) by the Q192R polymorphism of the PON1 gene in order to identify their genetic predisposition to dyslipidemia and atherosclerosis, as well as to determe the possibility of correcting the reduced activity of the PON1 enzyme in the examined individuals by the complex drug Cytoflavin. MATERIAL AND METHODS: The study included 25 men with advanced POAG, IOP compensated by hypotonic agents, and 20 volunteers without POAG (mean age 63.0±5.4 years). All subjects underwent genotyping by the Q192R polymorphism of the PON1 gene using an analyzer. PON1 activity was assessed by the rate of nitrophenol formation when paraoxone diluted in acetone was added to the blood plasma. At the second stage, patients (of different phenotypes) were prescribed the complex drug Cytoflavin. RESULTS: Homozygous carriers of the 192R allele were found to have significantly lower levels of PON1 activity than homozygous carriers of the Q192 allele. Carriage of the 192R allele may determine an increased risk of atherosclerotic injury in patients with POAG, especially in cases with high levels of atherogenic blood lipoproteins, low levels of high-density lipoproteins, or high levels of peroxidized lipids in the blood. The drug Cytoflavin showed a positive therapeutic effect on oxidative stress and hypercholesterinemia in POAG patients. CONCLUSION: These findings can be used to determine the atherogenicity of lipoproteins and the progression of glaucomatous optic neuropathy and to optimize the therapy of PAHO.

[Structural and functional features of peripheral vasculature in patients with glaucoma]. / Strukturno-funktsional'nye osobennosti perifericheskikh sosudov pri glaukome.

PURPOSE: To study the reactivity of the vascular endothelium and the elastic properties of the upper and lower extremities, and assess the vascular innervation effect of Cytoflavin in patients with stable and rapidly progressive primary open-angle glaucoma (POAG). MATERIAL AND METHODS: The study included 67 patients with POAG (mean age 66.3±1.5 years), among them 31 with stable and 36 with rapidly progressive glaucoma. During the first stage of the study, the reactivity of the vascular endothelium was assessed with reactive hyperemia test; the viscoelastic properties of the upper and lower extremities were evaluated using volumetric sphygmomanometry. For the second stage of the study, patients were divided into the main group (n=20) that received intravenous injections of 10 ml Cytoflavin with 200 ml of 5% glucose solution for 10 days and then 2 tablets twice a day for 60 days, and the control group (n=16). RESULTS: The function of the vascular endothelium was significantly reduced in patients with rapidly progressive POAG. Correlation analysis revealed a negative correlation between the flow-dependent vasodilation (FDV), and the duration of POAG and initial diameter of the brachial artery (r=0.5, p<0.05 and r=0.6, p<0.05, respectively). Pathological response of vessel endothelium was detected in 88% of patients with stable and 96% of patients with rapidly progressive POAG. Cytoflavin was found to have positive effects on the endothelium in patients with POAG. CONCLUSION: The obtained data can be used for identification of risk factors for rapid POAG progression and optimization of its treatment.