Increased Systemic Oxidative Stress and DNA Damage in Patients with Exudative Age-Related Macular Degeneration
Abstract
Amaç: Bu çalışmanın
amacı eksudatif yaşa bağlı makula dejenerasyonu (YBMD) olan hastalarda sistemik
oksidatif stres ve genotoksisite (DNA hasarı) bulgularını araştırmaktır.
Materyal-metod:
Çalışmaya eksudatif YBMD'li 26 hasta (68.9±1.9 yaş) ve 26 yaş ve cinsiyet
uyumlu (64.8±2.2 yaş) sağlıklı kontrol grubu (p=0.268, p=0.258) alındı. Serum total
antioksidan durumu (TAS) ve total oksidan durumu (TOS) ticari bir kit
kullanılarak ölçüldü. Oksidatif stres indeksi (OSİ) hesaplandı. DNA hasarı,
venöz tam kandan lenfosit izolasyonunu takiben Comet (kuyruklu yıldız) analizi
kullanılarak değerlendirildi. Kuyruk uzunluğu (TL) ve kuyruk momenti (TM) dahil
olmak üzere parametreler, DNA hasarının kantitatif analizi için
değerlendirildi.
Bulgular: YBMD grubunda
kontrol grubuna göre daha düşük TAS ve daha yüksek OSİ değerleri mevcut iken,
TOS değerleri iki grup arasında farklılık göstermedi (p=0.006, p=0.039, p=0.319,
sırasıyla). Ayrıca, YBMD grubunda TL (p<0.0001) ve TM (p=0.005) kontrol
grubuna göre anlamlı olarak yüksek bulundu.
Sonuç: Eksudatif YBMD
hastalarında sistemik oksidatif stres indeksinin ve DNA hasarının daha yüksek
olduğu görülmektedir.
Keywords
References
- 1. Seddon JM. Macular Degeneration Epidemiology: Nature-Nurture, Lifestyle Factors, Genetic Risk, and Gene-Environment Interactions-The Weisenfeld Award Lecture Invest Ophthalmol Vis Sci 2017; 58(14): 6513-28.
- 2. Gorusupudi A, Nelson K, Bernstein PS. The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration. Adv Nutr 2017; 8(1): 40-53.
- 3. Datta S, Cano M, Ebrahimi K, Wang L, Handa JT. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD. Prog Retin Eye Res 2017; 60: 201-18
- 4. Du Z, Wu X, Song M, Li P, Wang L. Oxidative damage induces MCP-1 secretion and macrophage aggregation in age-related macular degeneration (AMD). Graefes Arch Clin Exp Ophthalmol 2016; 254(12): 2469-76.
- 5. Elbay A, Ozer OF, Akkan JC, Celik U, Kutlutürk I, Koytak A, et al. Comparison of serum thiol-disulphide homeostasis and total antioxidant-oxidant levels between exudative age-related macular degeneration patients and healthy subjects. Int Ophthalmol 2017; 37(5): 1095-101.
- 6. Uğurlu N, Aşık MD, Yülek F, Cagil N. Oxidative stress and anti-oxidative defence in patients with age-related macular degeneration. Curr Eye Res 2013; 38: 497-502.
- 7. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38: 1103-11.
- 8. Horoz M, Bolukbas C, Bolukbas FF, Aslan M, Koylu AO, Selek S, et al. Oxidative stress in hepatitis C infected end-stage renal disease subjects. BMC Infect Dis 2006; 6: 114.
- 9. Regulski MJ. Cellular Senescence: What, Why, and How. Wounds 2017; 29(6): 168-74.
- 10. Menck CF, Munford V. DNA repair diseases: What do they tell us about cancer and aging? Genet Mol Biol 2014; 37(1 Suppl): 220-33.
- 11. Szaflik JP, Janik-Papis K, Synowiec E, Ksiazek D, Zaras M, Wozniak K, et al. DNA damage and repair in age-related macular degeneration. Mutat Res 2009; 669: 169-76.
- 12. Wozniak K, Szaflik JP, Zaras M, Sklodowska A, Janik-Papis K, Poplawski TR, et al. DNA damage/repair and polymorphism of the hOGG1 gene in lymphocytes of AMD patients. J Biomed Biotechnol 2009; 2009: 827562.
- 13. Kumaravel TS, Vilhar B, Faux SP, Jha AN. Comet Assay measurements: a perspective. Cell Biol Toxicol 2009; 25: 53-64.
- 14. Collins AR. The comet assay for DNA damage and repair: principles, applications, and limitations Mol Biotechnol 2004; 26: 249-61.
- 15. Xu B, Kang L, Zhang G, Wu J, Zhu R, Yang M, et al. The changes of 8-OHdG, hOGG1, APE1 and Pol β in lenses of patients with age-related cataract. Curr Eye Res 2015; 40(4): 378-85.
- 16. Valavanidis A, Vlachogianni T, Fiotakis C. 8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2009; 27: 120-39.
- 17. Visvardis EE, Tassiou AM, Piperakis SM Study of DNA damage induction and repair capacity of fresh and cryopreserved lymphocytes exposed to H2O2 and gamma-irradiation with the alkaline comet assay Mutat Res 1997; 383: 71-80.
- 18. Nandhakumar S, Parasuraman S, Shanmugam MM, Rao KR, Chand P, Bhat BV. Evaluation of DNA damage using single-cell gel electrophoresis (Comet Assay). J Pharmacol Pharmacother 2011; 2: 107-11.
- 19. Singh NP, Stephens RE, Schneider EL. Modifications of alkaline microgel electrophoresis for sensitive detection of DNA damage. Int J Radiat Biol 1994; 66: 23-8.
- 20. Sachdeva MM, Cano M, Handa JT. Nrf2 signaling is impaired in the aging RPE given an oxidative insult. Exp Eye Res 2014; 119: 111-4.
- 21. Dinc E, Ayaz L, Kurt AH. Protective Effect of Combined Caffeic Acid Phenethyl Ester and Bevacizumab Against Hydrogen Peroxide-Induced Oxidative Stress in Human RPE Cells Curr Eye Res 2017; 42: 1659-66.
- 22. Mozaffarieh M, Schoetzau A, Sauter M, Grieshaber M, Orgül S, Golubnitschaja O, Flammer J, et al. Comet assay analysis of single-stranded DNA breaks in circulating leukocytes of glaucoma patients Mol Vis 2008; 14: 1584-8.
- 23. Singh NP. The comet assay: Reflections on its development, evolution and applications Mutat Res Rev Mutat Res 2016; 767: 23-30.
- 24. Mozaffarieh M, Schötzau A, Josifova T, Flammer J. The effect of ranibizumab versus photodynamic therapy on DNA damage in patients with exudative macular degeneration Mol Vis 2009; 15: 1194-9.
- 25. Lee E, Oh E, Lee J, Sul D, Lee J. Use of the tail moment of the lymphocytes to evaluate DNA damage in human biomonitoring studies Toxicol Sci 2004; 81: 121-32.
- 26. Ashby J, Tinwell H, Lefevre PA, Browne MA. The single cell gel electrophoresis assay for induced DNA damage (comet assay): measurement of tail length and moment Mutagenesis 1995; 10: 85-90.
Abstract
Objective: The purpose of this study was to investigate the
evidence of systemic oxidative stress and genotoxicity (DNA damage) in patients
with exudative age-related macular degeneration (AMD).
Material
-Method: The study comprised
26 patients with exudative AMD (68.9±1.9 years of age) and 26 age- and
sex-matched (64.8±2.2 years of age) healthy controls (p=0.268, p=0.258,
respectively). Serum total
antioxidant status (TAS) and total oxidant status (TOS) were measured with a
commercial kit. Oxidative stress index (OSI) was calculated. DNA damage was evaluated
using comet analysis following lymphocyte isolation from venous blood.
Parameters including tail length (TL) and tail moment (TM) were evaluated for
quantitative analysis of DNA damage.
Results:
The AMD group had lower TAS and
higher OSI values than in the control group, while TOS values did not differ
between the two groups (p=0.006, p=0.039, p=0.319, respectively). Furthermore,
TL (p<0.0001) and TM (p=0.005) were significantly higher in the AMD group
compared to the control group.
Conclusion:
Systemic oxidative stress index and
cumulative DNA damage appear to be increased in patients with exudative AMD.
Keywords
References
- 1. Seddon JM. Macular Degeneration Epidemiology: Nature-Nurture, Lifestyle Factors, Genetic Risk, and Gene-Environment Interactions-The Weisenfeld Award Lecture Invest Ophthalmol Vis Sci 2017; 58(14): 6513-28.
- 2. Gorusupudi A, Nelson K, Bernstein PS. The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration. Adv Nutr 2017; 8(1): 40-53.
- 3. Datta S, Cano M, Ebrahimi K, Wang L, Handa JT. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD. Prog Retin Eye Res 2017; 60: 201-18
- 4. Du Z, Wu X, Song M, Li P, Wang L. Oxidative damage induces MCP-1 secretion and macrophage aggregation in age-related macular degeneration (AMD). Graefes Arch Clin Exp Ophthalmol 2016; 254(12): 2469-76.
- 5. Elbay A, Ozer OF, Akkan JC, Celik U, Kutlutürk I, Koytak A, et al. Comparison of serum thiol-disulphide homeostasis and total antioxidant-oxidant levels between exudative age-related macular degeneration patients and healthy subjects. Int Ophthalmol 2017; 37(5): 1095-101.
- 6. Uğurlu N, Aşık MD, Yülek F, Cagil N. Oxidative stress and anti-oxidative defence in patients with age-related macular degeneration. Curr Eye Res 2013; 38: 497-502.
- 7. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38: 1103-11.
- 8. Horoz M, Bolukbas C, Bolukbas FF, Aslan M, Koylu AO, Selek S, et al. Oxidative stress in hepatitis C infected end-stage renal disease subjects. BMC Infect Dis 2006; 6: 114.
- 9. Regulski MJ. Cellular Senescence: What, Why, and How. Wounds 2017; 29(6): 168-74.
- 10. Menck CF, Munford V. DNA repair diseases: What do they tell us about cancer and aging? Genet Mol Biol 2014; 37(1 Suppl): 220-33.
- 11. Szaflik JP, Janik-Papis K, Synowiec E, Ksiazek D, Zaras M, Wozniak K, et al. DNA damage and repair in age-related macular degeneration. Mutat Res 2009; 669: 169-76.
- 12. Wozniak K, Szaflik JP, Zaras M, Sklodowska A, Janik-Papis K, Poplawski TR, et al. DNA damage/repair and polymorphism of the hOGG1 gene in lymphocytes of AMD patients. J Biomed Biotechnol 2009; 2009: 827562.
- 13. Kumaravel TS, Vilhar B, Faux SP, Jha AN. Comet Assay measurements: a perspective. Cell Biol Toxicol 2009; 25: 53-64.
- 14. Collins AR. The comet assay for DNA damage and repair: principles, applications, and limitations Mol Biotechnol 2004; 26: 249-61.
- 15. Xu B, Kang L, Zhang G, Wu J, Zhu R, Yang M, et al. The changes of 8-OHdG, hOGG1, APE1 and Pol β in lenses of patients with age-related cataract. Curr Eye Res 2015; 40(4): 378-85.
- 16. Valavanidis A, Vlachogianni T, Fiotakis C. 8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2009; 27: 120-39.
- 17. Visvardis EE, Tassiou AM, Piperakis SM Study of DNA damage induction and repair capacity of fresh and cryopreserved lymphocytes exposed to H2O2 and gamma-irradiation with the alkaline comet assay Mutat Res 1997; 383: 71-80.
- 18. Nandhakumar S, Parasuraman S, Shanmugam MM, Rao KR, Chand P, Bhat BV. Evaluation of DNA damage using single-cell gel electrophoresis (Comet Assay). J Pharmacol Pharmacother 2011; 2: 107-11.
- 19. Singh NP, Stephens RE, Schneider EL. Modifications of alkaline microgel electrophoresis for sensitive detection of DNA damage. Int J Radiat Biol 1994; 66: 23-8.
- 20. Sachdeva MM, Cano M, Handa JT. Nrf2 signaling is impaired in the aging RPE given an oxidative insult. Exp Eye Res 2014; 119: 111-4.
- 21. Dinc E, Ayaz L, Kurt AH. Protective Effect of Combined Caffeic Acid Phenethyl Ester and Bevacizumab Against Hydrogen Peroxide-Induced Oxidative Stress in Human RPE Cells Curr Eye Res 2017; 42: 1659-66.
- 22. Mozaffarieh M, Schoetzau A, Sauter M, Grieshaber M, Orgül S, Golubnitschaja O, Flammer J, et al. Comet assay analysis of single-stranded DNA breaks in circulating leukocytes of glaucoma patients Mol Vis 2008; 14: 1584-8.
- 23. Singh NP. The comet assay: Reflections on its development, evolution and applications Mutat Res Rev Mutat Res 2016; 767: 23-30.
- 24. Mozaffarieh M, Schötzau A, Josifova T, Flammer J. The effect of ranibizumab versus photodynamic therapy on DNA damage in patients with exudative macular degeneration Mol Vis 2009; 15: 1194-9.
- 25. Lee E, Oh E, Lee J, Sul D, Lee J. Use of the tail moment of the lymphocytes to evaluate DNA damage in human biomonitoring studies Toxicol Sci 2004; 81: 121-32.
- 26. Ashby J, Tinwell H, Lefevre PA, Browne MA. The single cell gel electrophoresis assay for induced DNA damage (comet assay): measurement of tail length and moment Mutagenesis 1995; 10: 85-90.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Original Article |
| Authors | |
| Publication Date | September 20, 2019 |
| Submission Date | April 12, 2019 |
| Published in Issue | Year 2019 Volume: 10 Issue: 3 |
SDÜ Sağlık Bilimleri Dergisi, makalenin gönderilmesi ve yayınlanması dahil olmak üzere hiçbir aşamada herhangi bir ücret talep etmemektedir. Dergimiz, bilimsel araştırmaları okuyucuya ücretsiz sunmanın bilginin küresel paylaşımını artıracağı ilkesini benimseyerek, içeriğine anında açık erişim sağlamaktadır.