Aging Clinical and Experimental Research

, Volume 24, Issue 1, pp 21–27 | Cite as

Association between oxidative stress and macromolecular damage in elderly patients with age-related macular degeneration

  • Isabella Venza
  • Maria Visalli
  • Maria Cucinotta
  • Diana TetiEmail author
  • Mario Venza
Original Article


Background and aims: The aim of the present study was to determine whether age and gender affect the imbalance between oxidant production and antioxidant levels in age-related macular degeneration (ARMD) patients. Methods: Total superoxide dismutase (T-SOD), total glutathione peroxidase (T-GSHPx), and catalase (CAT) activities, as well as malondialdehyde (MDA), protein carbonyl (PC), 8-Hydroxy-29-deoxyguanosine (8-OHdG) and total oxidation status (TOS) levels, were measured in the following groups subdivided by age and gender: 156 early-ARMD patients; 80 wet-late ARMD patients; 72 dry-late ARMD patients; and 207 healthy controls. Results: Among all study participants, women aged 50–54 had higher T-SOD and T-GSHPx activities and lower MDA, PC, TOS and 8-OHdG levels than age-matched men (p<0.05), whereas older women were not significantly different from age-matched older men. Significantly increased oxidative damage was associated with ARMD patients >60 years of age in both sexes compared with controls (p<0.01 for 60–64 and 65–69-year-old ARMD subgroups; p<0.001 for 70–74 and 75–80-year-old ARMD subgroups). Multiple regression analysis demonstrates that age significantly affects antioxidant status and oxidative damage in ARMD patients compared with controls (controls, p<0.05; ARMD patients, p<0.001). A direct correlation with antioxidant enzyme activities and an inverse correlation with oxidative DNA, protein and lipid damage were also observed in premenopausal women (controls, p<0.05; ARMD patients, p<0.001). Conclusions: Aging and postmenopausal status may be aggravating factors contributing to redox imbalance and oxidative damage in ARMD patients.

Key words

Aging age-related macular degeneration antioxidant/pro-oxidant balance gender macromolecular damage menopause 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Friedman DS, O’Colmain BJ, Munoz B et al. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 2004; 122: 564–72.PubMedCrossRefGoogle Scholar
  2. 2.
    Smith W, Mitchell P, Wang JJ. Gender, oestrogen, hormone replacement and age-related macular degeneration: results from the Blue Mountains Eye Study. Aust NZ J Ophthalmol 1997; 25: S13–5.CrossRefGoogle Scholar
  3. 3.
    Javitt JC, Zhou Z, Maguire MG, Fine SL, Willke RJ. Incidence of exudative age-related macular degeneration among elderly Americans. Ophthalmology 2003; 110: 1534–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Beatty S, Koh HH, Phil M, Henson D, Boulton M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 2000; 45: 115–34.PubMedCrossRefGoogle Scholar
  5. 5.
    Winkler BS, Boulton ME, Gottsch JD, Sternberg P. Oxidative damage and age-related macular degeneration. Mol Vision 1999; 5: 32–43.Google Scholar
  6. 6.
    Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP. Oxidative damage and protection of the RPE. Prog Retinal Eye Res 2000; 19: 205–21.CrossRefGoogle Scholar
  7. 7.
    Beckman KB, Ames BN. The free radical theory of aging matures. Physiol Rev 1998; 78: 547–81.PubMedGoogle Scholar
  8. 8.
    Miceli MV, Liles MR, Newsome DA. Evaluation of oxidative processes in human pigment epithelial cells associated with retinal outer segment phagocytosis. Exp Cell Res 1994; 214: 242–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Bailey T A, Kanuga N, Romero IA, Greenwood J, Luther PJ, Cheetham ME. Oxidative stress affects the junctional integrity of retinal pigment epithelial cells. Invest Ophthalmol Visual Sci 2004; 45: 675–84.CrossRefGoogle Scholar
  10. 10.
    Baynes JW. The Maillard hypothesis on aging: time to focus on DNA. Ann NY Acad Sci 2002; 959: 360–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Szaflik JP, Janik-Papis K, Synowiec E et al. DNA damage and repair in age-related macular degeneration. Mutat Res 2009; 669: 169–76.PubMedCrossRefGoogle Scholar
  12. 12.
    Totan Y, Yagci R, Bardak Y et al. Oxidative macromolecular damage in age-related macular degeneration. Curr Eye Res 2009; 34: 1089–93.PubMedCrossRefGoogle Scholar
  13. 13.
    Bird AC, Bressler NM, Bressler SB et al. An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv Ophthalmol 1995; 39: 367–74.PubMedCrossRefGoogle Scholar
  14. 14.
    Currie MS, Vala M, Pisetsky DS et al. Correlation between erythrocyte CR reduction and other blood proteinase markers in patients with malignant and inflammatory disorders. Blood 1990; 75: 1699–704.PubMedGoogle Scholar
  15. 15.
    Marklund SL, Holme E, Heller L. Superoxide dismutase in extracellular fluids. Clin Chim Acta 1982; 126: 41–51.PubMedCrossRefGoogle Scholar
  16. 16.
    Marklund SL. Extracellular superoxide dismutase in human tissues and human cell lines. J Clin Invest 1984; 74: 1398–403.PubMedCrossRefGoogle Scholar
  17. 17.
    Takahashi K, Cohen HJ. Selenium-dependent glutathione peroxidase protein and activity: immunological investigations on cellular and plasma enzymes. Blood 1986; 68: 640–5.PubMedGoogle Scholar
  18. 18.
    Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Guemouri L, Artur Y, Herbeth B, Jeandel C, Cuny G, Siest G. Biological variability of superoxide dismutase, glutathione peroxidase, and catalase in blood. Clin Chem 1991; 37: 1932–7.PubMedGoogle Scholar
  20. 20.
    Lowry OH, Rosenbrough NJ, Farr AL. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265–75.PubMedGoogle Scholar
  21. 21.
    Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34: 497–500.PubMedGoogle Scholar
  22. 22.
    Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70: 158–69.PubMedGoogle Scholar
  23. 23.
    Valenzuela A. The biological significance of malondialdehyde determination in the assessment of tissue oxidative stress. Life Sci 1991; 48: 301–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Levine RL, Garland D, Oliver CN et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 1990; 186: 464–78.PubMedCrossRefGoogle Scholar
  25. 25.
    Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38: 1103–11.PubMedCrossRefGoogle Scholar
  26. 26.
    Evereklioglu C, Er H, Doganay S et al. Nitric oxide and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in patients with age-related macular degeneration. Doc Ophthalmol 2003; 106: 129–36.PubMedCrossRefGoogle Scholar
  27. 27.
    Nowak M, Swietochowska E, Wielkoszynski T et al. Changes in blood antioxidants and several lipid peroxidation products in women with age-related macular degeneration. Eur J Ophthalmol 2003; 13: 281–6.PubMedGoogle Scholar
  28. 28.
    Mares-Perlman JA, Klein R, Klein BE et al. Association of zinc and antioxidant nutrients with age-related maculopathy. Arch Ophthalmol 1996; 114: 991–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Gautam N, Das S, Mahapatra SK, Chakraborty SP, Kundu PK, Roy S. Age associated oxidative damage in lymphocytes. Oxid Med Cell Longev 2010; 3: 275–82.PubMedCrossRefGoogle Scholar
  30. 30.
    Mendoza-Núñez VM, Beristain-Pérez A, Pérez-Vera SP, Altamirano-Lozano MA. Age-related sex differences in glutathione peroxidase and oxidative DNA damage in a healthy Mexican population. J Womens Health (Larchmt) 2010; 19: 919–26.CrossRefGoogle Scholar
  31. 31.
    Wang AL, Lukas TJ, Yuan M, Du N, Handa JT, Neufeld AH. Changes in retinal pigment epithelium related to cigarette smoke: possible relevance to smoking as a risk factor for age-related macular degeneration. PLoS One 2009; 4: e5304.PubMedCrossRefGoogle Scholar
  32. 32.
    Miquel J, Ramírez-Boscá A, Ramírez-Bosca JV, Alperi JD. Menopause: a review on the role of oxygen stress and favorable effects of dietary antioxidants. Arch Gerontol Geriatr 2006; 42: 289–306.PubMedCrossRefGoogle Scholar
  33. 33.
    Baeza I, Fdez-Tresguerres J, Ariznavarreta C, De la Fuente M. Effects of growth hormone, melatonin, oestrogens and phytoestrogens on the oxidized glutathione (GSSG)/reduced glutathione (GSH) ratio and lipid peroxidation in aged ovariectomized rats. Biogerontology 2010; 11: 687–701.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Internal Publishing Switzerland 2012

Authors and Affiliations

  • Isabella Venza
    • 1
  • Maria Visalli
    • 1
  • Maria Cucinotta
    • 2
  • Diana Teti
    • 2
    Email author
  • Mario Venza
    • 3
  1. 1.Department of Surgical SpecialitiesAzienda Ospedaliera Universitaria G. MartinoMessinaItaly
  2. 2.Department of Experimental Pathology and Microbiology, Section of Experimental Pathology, Torre Biologica (IV p.)Azienda Ospedaliera Universitaria G. MartinoMessinaItaly
  3. 3.Department of OdontostomatologyAzienda Ospedaliera Universitaria G. MartinoMessinaItaly

Personalised recommendations