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ABSTRACT: Abstract Background: It has been suggested that the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in the degradation of extracellular matrix components, resulting in ocular tissue damage. The -735C/T and -1306C/T polymorphisms recognized in the promoter region of the MMP-2 gene resulting in its expression level were investigated in association with the development of primary open-angle glaucoma (POAG) in a Polish population. Methods: DNA samples collected from 271 patients with POAG and 281 healthy controls were used in this study. Polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Clinical parameters of the rim area (RA) and retinal neuron fiber layer (RNFL) were also analyzed. Results: We found that the -735C/T and -1306C/T polymorphisms of MMP-2 were not associated with a risk of POAG. However, both the -735T/T (OR = 0.18 (0.04-0.92) p = 0.03) and the -1306T/T (OR = 0.14 (0.03-0.67) p = 0.007) genotypes of MMP-2 were significantly associated with the rim area factor in early stage of POAG suggesting its protective role in the disease progression. Conclusion: Finally, our data suggest that gene polymorphisms of MMP-2 may have a protective role in the progression of primary open-angle glaucoma in a Polish population.
Ophthalmic Genetics 05/2013; · 0.93 Impact Factor
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ABSTRACT: PURPOSE:: To investigate the association between the g.4235T>C (rs2337395) polymorphism of the UNG gene and the c.-31A>G (rs3087404) polymorphism of the SMUG1 gene and the risk of age-related macular degeneration (AMD), as well as modulation of this association by some environmental and lifestyle factors. METHODS:: Overall, 272 AMD patients and 105 control subjects were enrolled in this study. Both polymorphisms were genotyped by restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP). RESULTS:: The C/C genotype of the g.4235T>C polymorphism of the UNG gene was associated with an increased risk of dry AMD (odds ratio, 2.54), whereas the T/T genotype of this polymorphism decreased such risk (odds ratio, 0.41). The presence of the T allele of the g.4235T>C polymorphism and the A allele of the c.-31A>G polymorphism of the SMUG1 gene (odds ratio, 2.17 and 2.18, respectively) was associated with an increased risk of AMD severity, expressed by the comparison of the frequencies of genotypes in the group of patients with wet AMD versus those with dry AMD. Conversely, the C/C genotype of the g.4235T>C polymorphism, the G/G genotype of the c.-31A>G polymorphism, and the C/C-G/G combined genotype of both polymorphisms had a protective effect (odds ratio, 0.48, 0.46, and 0.18; respectively). CONCLUSION:: The results obtained suggest the potential role of the g.4235T>C and the c.-31A>G polymorphisms in AMD pathogenesis.
Retina (Philadelphia, Pa.) 05/2013; · 2.93 Impact Factor
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ABSTRACT: BACKGROUND: Numerous data have shown that progressive loss of human trabecular meshwork (TM) cells may be connected with oxidative stress. This suggests an association of base-excision repair with the risk for development of primary open-angle glaucoma (POAG). PURPOSE: The aim of this study was to evaluate the role of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326SerCys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of POAG. METHODS: Our research included 170 patients with POAG and 193 healthy controls. Gene polymorphisms were investigated by PCR-RFLP. The Heidelberg Retinal Tomography (HRT) clinical parameters were also analyzed. RESULTS: The 399Arg/Gln genotype of the XRCC1 gene was associated with an increased risk for POAG (OR 2.50; 95% CI, 1.54-4.07, P=0.0002). The 399Gln/Gln XRCC1 genotype may increase the risk for POAG progression according to clinical parameters such as cup/disk ratio (c/d) (OR 1.93; 95% CI, 1-3.73, P=0.04) and Rim area (RA factor) (OR 3.88; 95% CI, 1.01-14.82, P=0.04). Moreover, an association was found of retinal nerve-fiber layer (RNFL factor) with the 399Arg/Gln XRCC1 genotype distribution and POAG progression (OR 2.46; 95% CI, 1.06-5.68, P=0.03). In contrast, analysis of the 324Gln/His MUTYH gene polymorphism distribution in the patient group according to RA factor showed that it may reduce the progression of POAG (OR 0.14; 95% CI, 0.02-0.89, P=0.05). Our current study demonstrates an association between the 326Ser/Cys OGG1 gene polymorphism and the 326Cys allele of the OGG1 gene, and progression of POAG. In addition, the presence of the 326His allele of the MUTYH gene may increase the risk for POAG progression, according to the VF parameter (OR 2.57; 95% CI, 1.47-4.57, P=0.0001). CONCLUSION: We suggest that the 399Arg/Gln genotype and the 399Gln allele of the XRCC1 gene may be risk factors for POAG development. Moreover, we postulate that the 399 Arg/Gln XRCC1, the 326 Ser/Cys OGG1 and the 324 Gln/His MUTYH genes polymorphisms may be associated with progression of POAG.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 03/2013; · 2.85 Impact Factor
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ABSTRACT: Fuchs endothelial corneal dystrophy (FECD) is a slowly progressive eye disease leading to blindness, mostly affecting people above 40 years old. The only known method of curing FECD is corneal transplantation. The disease is characterized by the presence of extracellular deposits called "cornea guttata", apoptosis of corneal endothelial cells, dysfunction of Descement's membrane and corneal edema. Oxidative stress is suggested to play a role in FECD pathogenesis. Reactive oxygen species produced during the stress may damage biomolecules, including DNA. In the present study we evaluated the extent of endogenous DNA damage, including oxidatively modified DNA bases, and damage induced by hydrogen peroxide as well as the kinetics of DNA repair in peripheral blood mononuclear cells of 50 patients with FECD and 43 age-matched controls without visual disturbances. To quantify DNA damage and repair we used the alkaline comet assay technique with the enzymes recognizing oxidative DNA damage, hOGG1 and EndoIII. We did not observe differences in the extent of endogenous and hydrogen peroxide-induced DNA damage between FECD patients and controls. However, we found a lower efficacy of DNA repair in FECD patients as compared with control individuals. The results obtained suggest that the lowering of the DNA repair capacity may be one of the mechanisms underlying the role of oxidative stress in the FECD pathology.
Molecular Biology Reports 12/2012; · 2.93 Impact Factor
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ABSTRACT: Age-Related Macular Degeneration (AMD) is an eye disease that results in progressive and irreversible loss of central vision and is considered as the primary cause of visual impairment, including blindness, in the elderly in industrialized countries. Oxidative stress has been implicated in the pathogenesis of AMD. The hOGG1 and the MUTYH genes play an important role in the repair of oxidatively damaged DNA in the base excision repair pathway. The DNA glycosylases encoded by the hOGG1 and MUTYH genes initiate this pathway by recognizing and removing 8-oxoguanine and adenine paired with 8-oxoguanine, respectively. Our study was designed to examine the association between the c.977C>G polymorphism (rs1052133) of the hOGG1 gene and the c.972G>C polymorphism (rs3219489) of the MUTYH gene and AMD as well as the modulation of this association by some clinical and lifestyle factors. Genotypes were determined in DNA from blood of 271 AMD patients, including 101 with wet and 170 with dry form of the disease and 105 sex- and age-matched individuals without AMD. We observed an association between AMD, dry and wet forms of AMD and the C/G genotype and the G allele of the c.977C>G-hOGG1 polymorphism (p 0.006; 0.009; 0.021 and 0.004; 0.005; 0.016 respectively). On the other hand, the C/C genotype and the C allele reduced the risk of AMD as well as of its dry form or wet form (p 0.002; 0.003; 0.010 and 0.004; 0.005; 0.016, respectively). Therefore, the associations we detected were driven by the dry AMD. We observed some statistically significant association between the occurrence of AMD and its dry and wet forms and genotypes of the other polymorphism, the c.972G>C-MUTYH polymorphism, but due to borderline character of all this association we do not consider them as medically relevant. Our findings suggest that the c.977C>G-hOGG1 polymorphism may be associated with dry AMD. Further studies are needed to determine possible association between AMD and the c.972G>C-MUTYH polymorphism.
Experimental Eye Research 03/2012; 98:58-66. · 3.26 Impact Factor
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ABSTRACT: Age-related macular degeneration (AMD) is an ocular disease affecting macula - the central part of the retina, resulting in the degeneration of photoreceptors and retinal epithelium and causing severe central vision impairment. The pathophysiology of the disease is not completely known, but a significant role is attributed to genetic factors. The contribution of oxidative stress in AMD as a trigger of the degenerative process is well-established. Iron ions may act as a source of reactive oxygen species; therefore, maintaining iron homeostasis is important for redox balance in the organism. Diversity in iron homeostasis genes may counterpart in unbalanced redox state, and thus be involved in AMD pathophysiology.
In this work, we searched for an association between some single nucleotide polymorphisms in the divalent metal transporter 1 (DMT1) gene intronic IVS4+44C>A (rs224589) and 3'-UTR c.2044T>C (rs2285230) and environmental factors and AMD. Genotyping was performed using the PCR-RFLP method. DNA was obtained from 436 AMD patients and 168 controls.
We did not find any association between the genotypes of the two polymorphisms and AMD occurrence. However, we observed that AMD patients living in a rural environment and having the CC genotype of the IVS4+44C>A polymorphism had an increased risk of AMD, while individuals with the CA genotype or the A allele had a decreased risk of the disease. Moreover, in male AMD patients the C allele increased the risk of the disease, while the AA genotype decreased it.
These results suggest that the VS4+44C>A polymorphism of the DMT1 gene may interact with place of living and gender to modulate the risk of AMD.
Albrecht von Graæes Archiv für Ophthalmologie 02/2012; 250(7):1057-65. · 2.17 Impact Factor
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ABSTRACT: Purpose: Limited knowledge exists about the influence of donor age and death-to-preservation interval (DPI) on the metabolic properties of the cornea. The aim of this study is to investigate the relationship between both factors and metabolite content of the cornea. Methods: Corneas from 15 human donors (age: 41-78 years) were obtained within 16 hrs post-mortem and kept in cold storage for 8 days. The metabolic profiles of the samples were investigated using high-resolution, magic angle spinning (1) H nuclear magnetic resonance spectroscopy before and after 8 days of preservation. Results: Twenty-two metabolites were detected and assigned in the corneal spectra. The significant metabolic differences before and after hypothermic storage were revealed between younger and older donors. DPI-related significant differences revealed before preservation of the corneas were not displayed after 8 days of cold storage. Conclusions: Age of donor as well as post-mortem time influences the biochemical properties of the cornea. Cold storage decreases the metabolite differences between the tissues collected at different post-mortem time.
Acta ophthalmologica 11/2011; · 2.44 Impact Factor
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ABSTRACT: Primary open angle glaucoma (POAG) is considered to be a leading cause of irreversible blindness worldwide. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) have been extensively studied as POAG risk factors. Recently, several single-nucleotide polymorphisms (SNPs) for MMPs and TIMPs encoding genes have been reported in POAG patients. The aim of this study was to investigate association of the -1607 1G/2G MMP1 and 372 T/C TIMP1 gene polymorphisms with risk of POAG in a Polish population.
In the present case-control study we examined a group of 449 unrelated Caucasian subjects consisting of 196 POAG patients (66 males and 130 females; mean age 70 ± 14) and 253 controls (72 males and 181 females; mean age 67 ± 16). The MMP1-1607 1G/2G and TIMP1 372 T/C gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated.
We found a statistically significant increase of the 2G/2G genotype (OR 1.73; 95% CI 1.05-2.86; p=0.019) as well as the 2G allele frequency (OR 1.34; 95% CI 1.03-1.75; p=0.017) of MMP1 in POAG patients in comparison to healthy controls. There were no differences in the genotype and allele distributions and odds ratios of the TIMP1 polymorphism between patients and controls group. We also did not find any association of TIMP1 with MMP1 gene-gene interaction and risk of POAG occurrence.
In conclusion, we suggest that the -1607 1G/2G polymorphism of MMP1 gene may be considered as an important risk factor associated with primary open angle glaucoma in a Polish population. However, further in vivo study is needed to evaluate biological importance of MMPs polymorphisms as a risk factor of POAG.
Medical science monitor: international medical journal of experimental and clinical research 07/2011; 17(7):CR417-21. · 1.70 Impact Factor
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ABSTRACT: Primary open-angle glaucoma (POAG) is the leading cause of blindness in the industrial countries. It is reported that oxidative stress might be an important risk factor in the pathogenesis of POAG. Forty subjects including 20 patients with open-angle glaucoma (9 men and 12 women, mean age 61.8±12.1yr) and 20 controls without glaucoma symptoms (9 men and 12 women, mean age 58.1±17.7yr) were enrolled in our study. The main aim of the work was to evaluate oxidative stress markers in the pathogenesis of open-angle glaucoma. In our work the activity of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) as well as the total antioxidant status (TAS) was estimated. An alkaline comet assay was used to measure DNA damage of strand breaks (SB), oxidized purines as glicosylo-formamido-glicosylase (Fpg) sites, and oxidized pirmidines as endonuclease III (Nth) sites. We measured endogenous as well as exogenous DNA damage after 10μM hydrogen peroxide treatment (H(2)O(2)). We did not observe any statistical changes of DNA strand break lesion in examined POAG patients according to healthy subjects (P>0.05). However, either endogenous (P<0.01) or exogenous (P<0.001) levels of oxidative DNA damage in POAG patients were found to be statistically higher than controls. A significant decrease of antioxidant enzymes: CAT (P<0.001), SOD (P<0.05), and GPX (P<0.001) and a non-statistical decrease of TAS status (P>0.05) in glaucoma patients according to controls were also indicated. In conclusion our data revealed that oxidative stress had a pathogenic role in primary open-angle glaucoma. Therefore, we suggested that the modulation of a pro-oxidant/antioxidant status might be a relevant target for glaucoma prevention and therapy.
Experimental and Molecular Pathology 01/2011; 90(2):231-7. · 2.42 Impact Factor
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Retina (Philadelphia, Pa.) 09/2010; 30(8):1328-9; author reply 1329. · 2.93 Impact Factor
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ABSTRACT: Glaucoma is typically an insidious-onset disease with serious visual consequences that has been positively linked to diabetes mellitus (DM). Glaucoma is more often present in the elderly. Important prognostic factors of glaucoma may be oxidative stress resulting from the toxic effects of glucose, and diabetes-associated vascular complications. Fifty-five patients and control subjects aged 71.0+/-10.1 yrs were enrolled in this study. Iris-tissue samples from DM type-2 patients, primary open-angle glaucoma-positive and -negative DM patients, and from healthy subjects were examined by use of the alkaline comet assay. We measured the DNA damage as numbers of strand breaks (SBs), oxidized purines as glycosyl-formamido-glycosylase (Fpg)-susceptible sites, and oxidized pyrimidines as endonuclease III (Nth)-susceptible sites. It was found that the level of oxidative damage in iris tissue was statistically higher in DM and glaucoma patients than that in healthy controls (oxidized purines: 38.0% and 34.7% vs 15.4%; oxidized pyrimidines: 43.3% and 39.0% vs 23.3%; P<0.001). Interestingly, we found strongly elevated levels of oxidized purines and pyrimidines in glaucomatous patients who also had DM, in comparison with healthy controls (oxidized purines: 55.7% vs 15.4%; oxidized pyrimidines: 61.8% vs 23.3%; P<0.001). Our observations suggest that the generation of reactive oxygen species may promote localized DNA damage in glaucoma-iris tissues of elderly patients vulnerable to diabetic injury.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 02/2010; 697(1-2):19-23. · 2.85 Impact Factor
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ABSTRACT: In this study we examined 264 people to estimate the prevalence of Demodex infection. The subjects were divided into 4 groups. First two groups consisted of young people (mean age 22 years) and seniors (mean age 66 years) respectively. The third group included people who work with microscopes (mean age 44 years). Forth group consisted of patients with diagnosed blepharitis (mean age 65 years). From every individual 3-4 lashes were epilated from the eyelids of both eyes and examined under the microscope for Demodex mites. The statistical analysis based on logistic regression was used to estimate the probability of infection. Age was independent variable significant for this model (p < 0.001). Significant relation between age and probability of Demodex infection was showed. The lowest number of infected individuals was observed in the group of young subjects (only 5%), the highest in the blepharitis patients (74% infected). Among microscope users 30% were infected, in the group of seniors 34% were infected.
Klinika oczna 01/2010; 112(10-12):307-10.
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ABSTRACT: The pathogenesis of age-related macular degeneration (AMD) is thought to be determined by an array of environmental and genetic factors. The association of increased expression of vascular endothelial growth factor (VEGF) with AMD, especially the wet form of AMD, was reported in several studies. The VEGF gene is highly polymorphic and some of its polymorphisms may affect its expression. In our work, we searched for an association between the -460C> (rs833061) and -634G>C (rs2010963) polymorphisms of the VEGF gene and the occurrence of AMD and its dry and wet forms. We have chosen these polymorphisms because they were shown to be significant in other studies and we previously showed their association with diabetic retinopathy. A total of 401 individuals were enrolled in this study: 136 controls, and 88 patients with dry and 177 with wet AMD. The polymorphisms were determined with DNA from peripheral blood lymphocytes by allele-specific and restriction fragment length polymorphism polymerase chain reaction. The significance of the polymorphisms was assessed by multiple logistic regression, producing odds ratios (ORs) and 95% confidence intervals (CIs). We observed a weak association (OR 2.90) between AMD occurrence and the C/T genotype of the -460C>T polymorphism. An association (OR 3.77) between the C/T genotype of the -460C>T polymorphism and the occurrence of dry AMD was observed. The T/T genotype considerably lowered the risk of dry AMD (OR 0.19). Dry AMD was associated with the C/C genotype of the -634G>C polymorphism (OR 3.68). Another weak association (OR 2.63) was found between the C/T genotype of the -460C>T polymorphism and the occurrence of wet AMD. The occurrence of AMD was correlated with the presence of the combined C/T-G/G genotype of both polymorphisms (OR 2.41), whereas the T/T-G/G and T/T-G/C genotypes exerted a protective effect against the disease (OR 0.22 and 0.48, respectively). The presence of the C/T-G/G and C/T-C/C combined genotypes increased the risk of dry AMD (OR 2.08 and 3.77, respectively), whereas the presence of the T/T-G/G and T/T-G/C genotypes decreased the risk (OR 0.15 and 0.28, respectively). In the wet form of AMD, the combined genotype C/T-G/G slightly favored the disease (OR 2.61) and the T/T-G/G genotype had a protective effect (OR 0.25). Analysis of haplotypes of both polymorphisms yielded similar results for AMD in general as well as for the dry and wet forms of the disease: the CG haplotype favored both forms of AMD, whereas the TG haplotype protected against both forms of AMD. The results obtained indicate that the -460C>T and -634G>C polymorphisms of the VEGF gene may be associated with the dry and wet forms of AMD in a Polish population.
Experimental and Molecular Pathology 09/2009; 87(3):234-8. · 2.42 Impact Factor
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ABSTRACT: Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was greater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 07/2009; 669(1-2):169-76. · 2.85 Impact Factor
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ABSTRACT: Azithromycin is a macrolide class antibiotic, recently adapted for topical use in ophthalmology. It is effective against the most frequent pathogens found in bacterial conjunctivitis, Gram positive and Gram negative bacteria. Azithromycin has the specificity to have sustained high tissue levels: after repeated instillation, it has been shown to reach sustained concentrations above the MICs of susceptible bacteria for 4 days in tears and for 7 days in conjunctiva.
To investigate the effectiveness and tolerance of treatment with Azithromycin 1.5% eye drops in bacterial conjunctivitis.
The prospective study included 40 patients (69 eyes) with purulent bacterial conjunctivitis; aged 21-70 years; average: 38.05 Patients were treated with 1.5% azithromycin eye drops topically twice-daily for 3 days. Conjunctival swabbings were taken at the 1st and the 7th +/- 1 day of the treatment. Effectiveness and tolerance of eye drops were assessed in 7th +/- 1 day from the beginning of the treatment.
Bacteriological cultures were positive before treatment in 34 eyes (49.28%), negative--35 eyes (50.72%). In 69 eyes with bacterial conjunctivitis the following microorganisms were identyfied (34 eyes): Streptococcus pneumoniae 23.53% (8 eyes), Staphyllococcus aureus 23.53% (8 eyes), Staphyllococcus epidermidis 20.59% (7 eyes), Haemophilus influenzae 17.65% (6 eyes), Morganella Morgani 2.94% (1 eye), Proteus mirabilis 2.94% (1 eye), Enterococcus species 2.94% (1 eye), Streptococcus viridians 2.94% (1 eye), Moraxella (Branhamella) catarrhalis 2.94% (1 eye). Positive bacteriological culture at the 7th day of treatment--2 eyes (1 eye--Staphyllococcus epidermidis MSCNS, 1 eye--Morganella Morgani). Clinical recovery or significant improvement were observed in 68 of 69 evaluated eyes.
Three-day topical therapy with azithromycin 1.5% eye drops is an effective and well tolerated therapy for purulent bacterial conjunctivitis.
Klinika oczna 02/2009; 111(1-3):46-9.
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ABSTRACT: To assess the association between genotypes and alleles of the C-460T polymorphism of the vascular endothelial growth factor (VEGF) gene and the risk of wet form of age-related macular degeneration (AMD).
100 patients with clinically diagnosed wet form of AMD and 104 healthy individuals were enrolled in this study. The patients were diagnosed by optical coherence tomography, fluorescein angiography and indocyanin green angiography. The allele-specific polymerase chain reaction was used to determine the genotypes of the C-460T polymorphism of the VEGF gene. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a logistic regression model to assess the assoctiation betweeen genotypes of the C-460T polymorphism and AMD occurrence.
A difference was observed in the genotype distributions between patients and controls. An association (OR 3.04, 95% CI 1.65-5.60) was found between wet form of AMD and the C/T genotype. On the other hand, the T/T genotype displayed the protective effect against the disease.
The C-460T polymorphism of the endothelial growth factor can be considered as a potential marker for the wet form of age-related macular degeneration.
Klinika oczna 02/2009; 111(4-6):125-7.
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ABSTRACT: Pseudoexfoliation syndrome is an age-related elastosis. The current pathogenetic concept describes PEX as an elastic microfibrillopathy involving TGF-betal, oxidative stress and impaired cellular protection mechanisms as a key pathogenetic factors. Extracellular PEX material is produced, aggregated and accumulated in the anterior segment of the eye. It is also present in the skin, lungs, liver and other visceral organs. These findings suggest that pseudoexfoliation syndrome is a systemic disorder. It is also associated with coronary artery disease, hypertension, Alzheimer's disease and other cardio-vascular problems. The pseudoexfoliation syndrome has been found to be associated with higher mean intraocular pressure, secondary open-angle glaucoma, mature and nuclear cataract. Ocular depositions of pseudoexfoliation material can lead to many intraocular complications. That's why special attention is required before, during and after surgery.
Klinika oczna 02/2009; 111(4-6):160-4.
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ABSTRACT: Oxidative stress is a major factor in the pathogenesis of age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells are prone to reactive oxygen species (ROS) arising during the stress due to intense oxygen metabolism and a high oxygen pressure. Additionally, the cells can be exposed to ROS as a consequence of accumulation of iron ions in these cells, sunlight exposure and tobacco smoke. There are several defense systems against RTF in the cell, including antioxidant enzymes, low-molecular weight antioxidants and DNA repair pathways. RPE cells display phagocytic activity towards outer segments of photoreceptors and this activity can be associated with additional oxidative stress since the segments are rich in long chain, polyunsaturated fatty acids (PUFA). The oxidation of PUFA leads to the production of additional ROS. Moreover, oxidized PUFA are not correctly cleaved in the lysosomes of RPE and are accumulated in the form of lipofuscin, which is deposited in Bruch's membrane in the form of drusen and in this way it stimulates immune responses, including phagocytosis, associated with the recruiting of macrophages and dendritic cells. In this time, RPE cells are exposed to ROS, produced in oxygen burst associated with phagocytosis. Further studies, both clinical/epidemiological and in vitro, are needed to better understand relationship between AMD and oxidative stress.
Klinika oczna 02/2009; 111(4-6):168-73.
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ABSTRACT: Iron can be involved in the pathogenesis of age-related macular degeneration (AMD) through the oxidative stress. In siderosis, exogenous iron can cause retinal degeneration which can be also associated with elevated retinal iron levels resulting in hereditary defects in iron homeostasis. Iron is transported into the retina by the endocytosis of iron complexed with transferrin and stored in complex with ferritin. The retinal pigmented epithelium and the neuroretinal vasculature serve as blood-retina barriers and disruption of homeostasis at these barriers may result in iron overload. There is firm experimental evidence that retinas of AMD patients contain more iron than retinas of the healthy subjects, but the question whether it is the reason or a consequence of AMD remains open. Excessive iron can cause damage to protein, lipids and DNA through the generation of free radicals in the Fenton reaction. Therefore, iron may play a role in the pathogenesis of AMD as a source of free radical damage but this hypothesis has not been verified experimentally and further studies are needed to establish the relationship between disturbance in iron homeostasis and AMD.
Klinika oczna 02/2009; 111(4-6):174-7.
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ABSTRACT: Oxidative stress is thought to play a role in the pathogenesis of age-related macular degeneration (AMD). We determined the extent of oxidative DNA damage and the kinetics of its removal as well as the genotypes of the Ser326Cys polymorphism of the hOGG1 gene in lymphocytes of 30 wet AMD patients and 30 controls. Oxidative DNA damage induced by hydrogen peroxide and its repair were evaluated by the comet assay and DNA repair enzymes. We observed a higher extent of endogenous oxidative DNA damage and a lower efficacy of its repair in AMD patients as compared with the controls. We did not find any correlation between the extent of DNA damage and efficacy of DNA repair with genotypes of the Ser326Cys polymorphism. The results obtained suggest that oxidative DNA damage and inefficient DNA repair can be associated with AMD and the variability of the hOOG1 gene may not contribute to this association.
Journal of Biomedicine and Biotechnology 01/2009; 2009:827562. · 2.44 Impact Factor
