Oxidative Stress, Diabetic Retinopathy, and Superoxide Dismutase 3

  • Larissa Ikelle
  • Muna I. Naash
  • Muayyad R. Al-UbaidiEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1185)


Diabetic retinopathy (DR) is a multifaceted disease, combining the deleterious effects of hyperglycemia and the propensity for accumulation of reactive oxygen species. Studies indicate that auto-oxidation of glucose, reduced antioxidant activity, and metabolic aberrations contribute to the pathogenesis of DR. These abnormalities stem from a fundamental imbalance between ROSs and antioxidant scavengers. To correct this imbalance and downstream effects, we propose that superoxide dismutase 3 (SOD3) is a viable therapeutic target for DR.


Antioxidant Diabetic retinopathy Superoxide Superoxide dismutase 3 Neovascularization Non-proliferative diabetic retinopathy Proliferative diabetic retinopathy Hydrogen peroxide Vitamin C Oxidative stress Hypoxia Macular edema 


  1. Al-Gubory KH, Fowler PA, Garrel C (2010) The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes. Int J Biochem Cell Biol 42:1634–1650CrossRefGoogle Scholar
  2. Batinic-Haberle I, Tovmasyan A et al (2014) SOD therapeutics: latest insights into their structure-activity relationships and impact on the cellular redox-based signaling pathways. Antioxid Redox Signal 20:2372–2415CrossRefGoogle Scholar
  3. Calderon GD, Juarez OH et al (2017) Oxidative stress and diabetic retinopathy: development and treatment. Eye 31:1122–1130CrossRefGoogle Scholar
  4. Chen B, Caballero S et al (2009) Delivery of antioxidant enzyme genes to protect against ischemia/reperfusion-induced injury to retinal microvasculature. Invest Ophthalmol Vis Sci 50:55877–55595Google Scholar
  5. Evans JL, Goldfine ID et al (2002) Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 42:599–622CrossRefGoogle Scholar
  6. Faraci FM, Didion SP (2004) Vascular protection superoxide dismutase isoforms in the vessel wall. Arterioscler Thromb Vasc Biol 24:1367–1373CrossRefGoogle Scholar
  7. García-Aguilar A, Cuezva JM (2018) A review of the inhibition of the mitochondrial ATP synthase by IF1 in vivo: reprogramming energy metabolism and inducing mitohormesis. Front Physiol 9:1322CrossRefGoogle Scholar
  8. Gast TJ, Fu X et al (2016) A computational model of peripheral photocoagulation for the prevention of progressive diabetic capillary occlusion. J Diabetes Res 2016:2508381CrossRefGoogle Scholar
  9. Gosbell AD, Stefanovic N (2006) Retinal light damage: structural and functional effects of the antioxidant glutathione peroxidase-1. Invest Ophthalmol Vis Sci 47:2613–2622CrossRefGoogle Scholar
  10. Hakki Kalkan I, Suher M (2013) The relationship between the level of glutathione impairment of glucose metabolism and complications of diabetes mellitus. Pak J Med 29:938–942Google Scholar
  11. Hartsock MJ, Cho H et al (2016) A mouse model of retinal ischemia-reperfusion injury through elevation of intraocular pressure. J Vis Exp (113)Google Scholar
  12. Juha P. Laurila, Lilja E. Laatikainen, Maria D. Castellone, Mikko O. Laukkanen, Eshel Ben-Jacob, (2009) SOD3 Reduces Inflammatory Cell Migration by Regulating Adhesion Molecule and Cytokine Expression. PLoS ONE 4 (6):e5786Google Scholar
  13. Klein JA, Ackerman SL (2003) Oxidative stress, cell cycle, and neurodegeneration. J Clin Investig 111:785–793CrossRefGoogle Scholar
  14. Kowluru RA, Chan PS (2007) Oxidative stress and diabetic retinopathy. Exp Diabetes Res 2007:43603PubMedPubMedCentralGoogle Scholar
  15. Laight DW, Carrier MJ, Anggard EE (2000) Antioxidants, diabetes and endothelial dysfunction. Cardiovasc Res 47:457–464CrossRefGoogle Scholar
  16. Laukkanen MO, Cammarota F et al (2015) Extracellular superoxide dismutase regulates the expression of small GTPase regulatory proteins GEFs, GAPs, and GDI. PLoS One 10(3):e0121441CrossRefGoogle Scholar
  17. Markus P. Schneider, Jennifer C. Sullivan, Paul F. Wach, Erika I. Boesen, Tatsuo Yamamoto, Tohru Fukai, David G. Harrison, David M. Pollock, Jennifer S. Pollock, (2010) Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury. Kidney International 78 (4):374-381Google Scholar
  18. Panfoli I, Calzia D et al (2012) Extra-mitochondrial aerobic metabolism in retinal rod outer segments: new perspectives in retinopathies. Med Hypotheses 78:423–427CrossRefGoogle Scholar
  19. Pattison DI, Rahmanto AS, Davies MJ (2012) Photo-oxidation of proteins. Photochem Photobiol Sci 11:38–53CrossRefGoogle Scholar
  20. Pham-Huy LA, He H, Pham-Huy C (2008) Free radicals, antioxidants in disease and health. Int J Biomed Sci 4:89–96. Retrieved from Scholar
  21. Rahimi N (2012) The ubiquitin-proteasome system meets angiogenesis. Mol Cancer Ther 11:538CrossRefGoogle Scholar
  22. Sahajpal NS, Goel RK et al (2018) Pathological perturbations in diabetic retinopathy: hyperglycemia, AGEs, oxidative stress and inflammatory pathways. Curr Protein Pept Sci 20:92CrossRefGoogle Scholar
  23. Seddon JM, Ajani UA et al (1994) Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. JAMA 272:1413–1420. Scholar
  24. Singh B, Bhat HK (2012) Superoxide dismutase 3 is induced by antioxidants, inhibits oxidative DNA damage and is associated with inhibition of estrogen-induced breast cancer. Carcinogenesis 33:2601–2610CrossRefGoogle Scholar
  25. Song H, Vijayasarathy C, Zeng Y, Marangoni D, Bush RA, Wu Z, Sieving PA (2016) NADPH oxidase contributes to photoreceptor degeneration in constitutively active RAC1 mice. Invest Ophthalmol Vis Sci 57:2864–2875CrossRefGoogle Scholar
  26. Usui S, Komeima K et al (2009) Increased expression of catalase and superoxide dismutase 2 reduces cone cell death in retinitis pigmentosa. Mol Ther 17:778–786CrossRefGoogle Scholar
  27. Young TA, Cunningham CC, Bailey SM (2002) Reactive oxygen species production by mitochondrial respiratory chain in isolated rat hepatocytes and liver mitochondria. Arch Biochem Biophys 405:65–72CrossRefGoogle Scholar
  28. Zeng H, Ding M et al (2014) Microglial NADPH oxidase activation mediates rod cell death in the retinal degeneration in rd mice. Neuroscience 275:54–61CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Larissa Ikelle
    • 1
  • Muna I. Naash
    • 1
  • Muayyad R. Al-Ubaidi
    • 1
    Email author
  1. 1.Department of Biomedical EngineeringUniversity of HoustonHoustonUSA

Personalised recommendations