Matrix metalloproteinases belong to an enzyme family, which assure a proteolysis of practically all components of the extracellular matrix of connective tissues in normal and pathological conditions. At physiological conditions, there are evidences on the impact of this enzyme group in the embryogenesis, morphogenesis, angiogenesis, and tissue involution. The activity impairment of matrix metalloproteinases and of their specific inhibitors leads to the biosynthesis misbalance and to the degradation of extracellular matrix components; it plays a role in the development of such diseases as diabetes mellitus, rheumatoid arthritis, and arteriosclerosis. Laboratory tests and clinical investigation results confirm the role of these enzymes in tissue remodeling of different eyeball structures in glaucoma (in particular, of the trabecular meshwork and the optic disc); it leads to intraocular fluid outflow impairment and to the glaucomatous optic neuropathy development. In the review, the analysis of clinical and experimental studies is performed that are dedicated to the investigation of matrix metalloproteinases role in the pathogenesis of different glaucoma types, of the possibility to use them as biomarkers, as well as therapeutic action targets in this disease.
Purpose. To study the main morphological features of the corneal endothelium in patients with pseudoexfoliative glaucoma (PEG). Methods. We included 193 subjects aged from 55 to 75 years. The main study group (PEG) included 96 patients (192 eyes), the primary open angle glaucoma (POAG) group included 36 patients (72 eyes) with POAG, the PEX group included 31 patients (62 eyes) with pseudoexfoliation syndrome without glaucoma. The control group consisted of 30 healthy subjects (60 eyes). Main corneal endothelium parameters were evaluated using a non-contact endothelial microscope EM-935 (Haag Streit, Switzerland). Data were analyzed by STATISTICA 9 software for Windows. Results. The patients with PEG had lower endothelial cell density (ECD) in comparison to the control group (p < 0.01), and PEX group (p < 0.05). The polymegatism level in patients with PEG and POAG was higher than in the control group (p < 0.001, and p < 0.01, correspondingly). In patients with moderate and advanced PEG, the ECD was significantly lower (p < 0.01), and the polymegatism level was significantly higher (p < 0.01) than the same parameters in patients with early PEG. The lowest ECD and the highest polymegatism percentage were observed in PEG patients with more pronounced PEX manifestations, p < 0.05. No effect of IOP-lowering eye drops on the corneal endothelium parameters was revealed, p < 0.05. Conclusions. Significant morphological changes of the corneal endothelium (decreased endothelial cell density, increased polymegatism percentage) were revealed in patients with PEG. It was established that the severity of these changes is associated with the PEG and PEX severity. No effect of IOP-lowering eye drops on the corneal endothelium parameters was detected.
Aim. To determine serum 25(OH)D and plasma MMP-2 and MMP-9 levels in patients with primary open-angle glaucoma (POAG), pseudoexfoliation glaucoma (PEG), and pseudoexfoliation syndrome (PES) - to assess potential associations between vitamin D status and these diseases. Methods. We included 238 patients (105 males and 133 females) aged from 55 to 75 years. One hundred twenty two patients had PEG, 46 patients had POAG, 32 had PES. 38 subjects were healthy, and were considered as the control group. Cases with clinically significant systemic diseases and concomiatant eye diseases were excluded, if there was a confirmed pathogenic impact of vitamin D and MMP. The serum 25(OH)D level was investigated by immunochemiluminescence method, plasma MMP-2 and MMP-9 levels - by ELISA. Results. Serum 25(OH)D level was between 4.6 and 82.25 nM/l (mean 41.7 nM/l), so most participants showed vitamin D deficiency. It was shown that mean serum 25(OH)D level in patients with PEG, POAG and PES was similar (39.3 ± 1.2, 38.8 ± 2.1 and 40.51 ± 2.4 nM/l, p > 0.05), but it was lower than that in the control group (52.7 ± 2.1 nM/l, p < 0.01). Plasma MMP-2 concentration was the same in all study groups. Plasma MMP-9 level was higher in POAG and PES patients (48.23 ± 3.26 and 54.01 ± 3.57 ng/ml) than in the control group (32.60 ± 2.34 ng/ml, p < 0.001) and PEG patients (40.86 ± 3.60 ng/ml, p < 0.05). We found positive correlations between MMP-2 and MMP-9 levels in patients with PEG (r = 0.48, p = 0.001) and patients with POAG (r = 0.43, p = 0.003). The correlation analysis showed also a negative relation between 25(OH)D and MMP-9 (r = -0.32, p = 0.02), MMP-2 (r = -0.33, p = 0.02) in patients with POAG. Summary. Study results confirmed a potential role of vitamin D in apoptosis regulation and tissue remodeling in patients with POAG and PES. Hence, vitamin D deficiency can be considered as a risk factor for glaucoma development.
Purpose. To study the possible association of 25-hydroxyvitamin D level, and vitamin D receptor (VDR) gene polymorphisms (BsmI, ApaI, TaqI, FokI) with pseudoexfoliative glaucoma (PEG) clinical manifestations. Methods. We examined 160 subjects (72 males (45%), and 88 females (55%)) aged from 55 to 75 years, residents of St. Petersburg and Leningrad region. 122 patients with PEG were enrolled in the main study group, the control group comprised 38 subjects without PEG, primary open angle glaucoma (POUG) and pseudoexfoliation syndrome (PES). 25(OH)D serum levels were assessed by chemiluminescent immunoassay (CLIA) method. Detection of VDR gene allele polymorphisms (ApaI, BsmI, FokI, and TaqI) was carried out using polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP) technique. Results. Patients with PEG had lower 25(OH)D serum levels compared to patients in the control group (39.3 ± 1.2 and 52.7 ± 2.1 nMol/l, respectively, p < 0.01). The prevalence of vitamin D deficiency was found to be higher among PEG patients than among healthy subjects (86.4% and 59.5%, respectively, p < 0.01). The prevalence of b allele (p < 0.001) and bb genotype (p < 0.001) (BsmI polymorphism), as well as of f allele and ff genotype (p < 0.05) (FokI polymorphism) in PEG patients were higher compared to healthy subjects. We found that the Fallele carriers (FokI polymorphism) had greater corneal thickness than the ff genotype carriers (547.3 ± 4.1 μm and 502.1 ± 25.8 μm, respectively, p < 0.01). It was revealed, that bb genotype, Bb genotype (BsmI polymorphism), and ff genotype (FokI polymorphism) were associated with the increased risk of PEG (OR = 8.2, CI 95%: 3.4-19.9; OR = 3.9, CI 95%: 1.7-9.0; OR = 2.3, CI 95%: 1.2-4.5, respectively). Conclusions. Results of this study for the first time ever showed the association between BsmI and FokI VDR gene polymorphisms and pseudoexfoliative glaucoma.
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