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<p>Macular degeneration MD is a chronic, lifestyle-related eye disease developing in increasingly younger people. The cause is not fully understood, but oxidative stress is among the most critical factors. The subject of our research is the wet form of MD. The tested materials were whole blood and plasma from 84 patients with exudative MD and from 127 healthy volunteers, from SW Poland. The concentration of toxic metals (Hg, Cd, Pb, As, Be), macroelements (Ca, Mg, Na, K, P) and microelements (Mn, Fe, Zn, Cu, Se, Mo, Cr, Li, V, Co, Ag, Ba, Ti, Tl, Sr, Al, Ni, Sn, B, Sb) was analyzed (ICP-MS) in the blood to determine environmental exposure. The activity of antioxidant enzymes (superoxide dismutase SOD, catalase CAT, glutathione peroxidase GPx, glutathione reductase GR) was determined to demonstrate the ability to eliminate the effects of reactive oxygen species ROS. The activity of nonenzymatic antioxidant mechanisms (reduced glutathione GSH, bilirubin, uric acid, vitamins A and E) was examined to assess the body’s ability to activate defense mechanisms against ROS. The intensity of lipoperoxidation (malondialdehyde, MDA), and the importance of ceruloplasmin CP in patients with exudative MD and their exposure to oxidative stress were determined. The presence of glutathione-S-transferase GST polymorphisms (<i>GSTT1</i>, <i>GSTM1</i>) was examined to determine their role in generating MD. The genetic polymorphism of interleukin-4 IL-4 and vascular endothelial growth factor VEGF-A was analyzed, and it was determined whether there is a genetic burden that can potentially increase the chance of developing MD. The activity of SOD, CAT, GPx, and GR, and the activity of nonenzymatic antioxidants (GSH, bilirubin, uric acid, all-trans retinol, and alpha-tocopherol) were determined using Cayman kits and HPLC chromatography. MDA was determined using Cayman reagents, and CP was determined using Wuhan reagents. In our exudative MD patients, P, Ca, Mn, Fe, Cu, and Zn were most involved in interactions, whereas in the control group, Pb, Ca, Mn, Zn, and Ba were most important. In the analysis of antioxidant parameters, significant differences were found between the studied groups for SOD, CAT, GPx, bilirubin, all-trans retinol, alpha-tocopherol, and uric acid. Also, MDA and CP showed significant differences. In MD patients and healthy individuals, many correlations were found. Significant differences were noted for <i>IL-4</i> in the frequency of the <i>T</i> allele in MD patients, and for Sr. The frequency distributions of <i>GSTT1</i> and <i>GSTM1</i> polymorphisms showed no significant differences between the groups, whereas differences were observed for all-trans retinol. Changes within <i>VEGF-A</i> genotypes showed no significant differences between the studied groups (p &gt; 0.5). Due to the presence of mutagenic substances in the environment, the changed genome plays an important role in MD development. The pathogenic process can be observed by analyzing the effectiveness of enzymatic and nonenzymatic mechanisms. The low diagnostic value of MDA and CP for patients with MD was indicated. The results highlighted the significant role of environmental factors and indicated new directions for research into MD etiology. They identified new parameters to be considered when examining predisposition to this disease (Na, P, Cr, Mn, Ba, MDA, bilirubin, A and E vitamins, SOD, CAT, GPx, IL-4). We compare the aspects we examine holistically, making this the first study of this type. Despite many elements of MD development being known so far, there are still many unanswered questions in this field that will require further analysis, especially regarding K, Pb, As, Hg, Cd, Sr, Al, Ba, V, Fe, mutations in <i>IL-4</i>, <i>GSTM1</i>, and <i>GSTT1</i>.</p>

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Macular degeneration dependent on defense mechanisms conditioned by chemical elements and genetic polymorphism

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月4日

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  • Piotr Kamiński,
  • Sylwia Brodzka,
  • Jędrzej Baszyński,
  • Rafał Paczała,
  • Emilia Stanek,
  • Katarzyna Rektor,
  • Renata Grochowalska,
  • Martin Hromada,
  • Tomasz Stuczyński,
  • Halina Tkaczenko,
  • Alina Woźniak,
  • Natalia Kurhaluk

摘要

Macular degeneration MD is a chronic, lifestyle-related eye disease developing in increasingly younger people. The cause is not fully understood, but oxidative stress is among the most critical factors. The subject of our research is the wet form of MD. The tested materials were whole blood and plasma from 84 patients with exudative MD and from 127 healthy volunteers, from SW Poland. The concentration of toxic metals (Hg, Cd, Pb, As, Be), macroelements (Ca, Mg, Na, K, P) and microelements (Mn, Fe, Zn, Cu, Se, Mo, Cr, Li, V, Co, Ag, Ba, Ti, Tl, Sr, Al, Ni, Sn, B, Sb) was analyzed (ICP-MS) in the blood to determine environmental exposure. The activity of antioxidant enzymes (superoxide dismutase SOD, catalase CAT, glutathione peroxidase GPx, glutathione reductase GR) was determined to demonstrate the ability to eliminate the effects of reactive oxygen species ROS. The activity of nonenzymatic antioxidant mechanisms (reduced glutathione GSH, bilirubin, uric acid, vitamins A and E) was examined to assess the body’s ability to activate defense mechanisms against ROS. The intensity of lipoperoxidation (malondialdehyde, MDA), and the importance of ceruloplasmin CP in patients with exudative MD and their exposure to oxidative stress were determined. The presence of glutathione-S-transferase GST polymorphisms (GSTT1, GSTM1) was examined to determine their role in generating MD. The genetic polymorphism of interleukin-4 IL-4 and vascular endothelial growth factor VEGF-A was analyzed, and it was determined whether there is a genetic burden that can potentially increase the chance of developing MD. The activity of SOD, CAT, GPx, and GR, and the activity of nonenzymatic antioxidants (GSH, bilirubin, uric acid, all-trans retinol, and alpha-tocopherol) were determined using Cayman kits and HPLC chromatography. MDA was determined using Cayman reagents, and CP was determined using Wuhan reagents. In our exudative MD patients, P, Ca, Mn, Fe, Cu, and Zn were most involved in interactions, whereas in the control group, Pb, Ca, Mn, Zn, and Ba were most important. In the analysis of antioxidant parameters, significant differences were found between the studied groups for SOD, CAT, GPx, bilirubin, all-trans retinol, alpha-tocopherol, and uric acid. Also, MDA and CP showed significant differences. In MD patients and healthy individuals, many correlations were found. Significant differences were noted for IL-4 in the frequency of the T allele in MD patients, and for Sr. The frequency distributions of GSTT1 and GSTM1 polymorphisms showed no significant differences between the groups, whereas differences were observed for all-trans retinol. Changes within VEGF-A genotypes showed no significant differences between the studied groups (p > 0.5). Due to the presence of mutagenic substances in the environment, the changed genome plays an important role in MD development. The pathogenic process can be observed by analyzing the effectiveness of enzymatic and nonenzymatic mechanisms. The low diagnostic value of MDA and CP for patients with MD was indicated. The results highlighted the significant role of environmental factors and indicated new directions for research into MD etiology. They identified new parameters to be considered when examining predisposition to this disease (Na, P, Cr, Mn, Ba, MDA, bilirubin, A and E vitamins, SOD, CAT, GPx, IL-4). We compare the aspects we examine holistically, making this the first study of this type. Despite many elements of MD development being known so far, there are still many unanswered questions in this field that will require further analysis, especially regarding K, Pb, As, Hg, Cd, Sr, Al, Ba, V, Fe, mutations in IL-4, GSTM1, and GSTT1.