Abstract
Purpose
To establish the effect of systemic oxidative stress on the pathogenesis of keratoconus by measuring serum total oxidant status (TOS) and total antioxidant status (TAS) in patients with keratoconus.
Methods
Twenty-five patients with keratoconus (keratoconus group) and 25 age–sex-matched healthy subjects (control group) were enrolled in the study. Exclusion criteria were smoking habit, history of any other corneal pathology, systemic disease or inflammation, and current antioxidant or anti-inflammatory therapies. All participants underwent a detailed ophthalmological examination and corneal topography. Serum samples were obtained from all participants. Oxidative stress markers (TAS and TOS) were measured using a commercial kit and oxidative stress index (OSI) was calculated.
Results
The study comprised 25 patients with keratoconus (mean age of 26.4±1.7 years) and 25 healthy control subjects (mean age of 26.6±1.7 years) (P>0.05). The serum TOS and OSI values were significantly higher in patients with keratoconus compared with those of the controls (P=0.036 and 0.037, respectively). However, serum TAS did not show significant difference between the keratoconus and control groups (P=0.497).
Conclusions
The higher levels of serum oxidant status and OSI in patients with keratoconus suggest that systemic oxidative stress might be involved in the pathogenesis of keratoconus.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Rabinowitz YS . Keratoconus. Surv Ophthalmol 1998; 42: 297–319.
Krachmer JH, Feder RS, Belin MW . Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol 1984; 28: 293–322.
Monnies CW . Abnormal rubbing and keractectasia. Eye Contact Lens 2007; 33: 265–271.
Buddi R, Lin B, Atilano SR, Zorapapel NC, Kenney MC, Brown DJ . Evidence of oxidative stress in human corneal diseases. J Histochem Cytochem 2002; 50: 341–351.
Arnal E, Peris-Martínez C, Menezo JL, Johnsen-Soriano S, Romero FJ . Oxidative stress in keratoconus? Invest Ophthalmol Vis Sci 2011; 52: 8592–8597.
Kenney MC, Brown DJ, Rajeev B . Everett Kinsey lecture. The elusive causes of keratoconus: a working hypothesis. CLAO J 2000; 26: 10–13.
Shoham A, Hadziahmetovic M, Dunaief JL, Mydlarski MB, Schipper HM . Oxidative stress in diseases of the human cornea. Free Radic Biol Med 2008; 45: 1047–1055.
Behndig A, Karlsson K, Johansson BO, Brannstrom T, Marklund SL . Superoxide dismutase isoenzymes in the normal and diseased human cornea. Invest Ophthalmol Vis Sci 2001; 42: 2293–2296.
Zhou L, Sawaguchi S, Twining SS, Sugar J, Feder RS, Yue BY . Expression of degradative enzymes and protease inhibitors in corneas with keratoconus. Invest Ophthalmol Vis Sci 1998; 39: 1117–1124.
Erel O . A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004; 37: 112–119.
Ferreira SM, Lerner SF, Brunzini R, Evelson PA, Llesuy SF . Oxidative stress markers in aqueous humor of glaucoma patients. Am J Ophthalmol 2004; 137: 62–69.
Erel O . A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38: 1103–1111.
Harma M, Harma M, Erel O . Increased oxidative stress in patients with hydatidiform mole. Swiss Med Wkly 2003; 133: 563–566.
Atilano SR, Coskun P, Chwa M, Jordan N, Reddy V, Le K et al. Accumulation of mitochondrial DNA damage in keratoconus corneas. Invest Ophthalmol Vis Sci 2005; 46: 1256–1263.
Chwa M, Atilano SR, Reddy V, Jordan N, Kim DW, Kenney MC . Increased stress-induced generation of reactive oxygen species and apoptosis in human keratoconus fibroblasts. Invest Ophthalmol Vis Sci 2006; 47: 1902–1910.
Chwa M, Atilano SR, Hertzog D, Zheng H, Langberg J, Kim DW et al. Hypersensitive response to oxidative stress in keratoconus corneal fibroblasts. Invest Ophthalmol Vis Sci 2008; 49: 4361–4369.
Gondhowiardjo TD, van Haeringen NJ . Corneal aldehyde dehydrogenase, glutathione reductase, and glutathione s-transferase in pathologic corneas. Cornea 1993; 12: 310–314.
Smith VA, Easty DL . Matrix metalloproteinase 2: involvement in keratoconus. Eur J Ophthalmol 2000; 10: 215–226.
Kenney MC, Chwa M, Atilano SR, Tran A, Carballo M, Saghizadeh M et al. Increased levels of catalase and cathepsin V/L2 but decreased TIMP-1 in keratoconus corneas: evidence that oxidative stress plays a role in this disorder. Invest Ophthalmol Vis Sci 2005; 46: 823–832.
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.
Udar N, Atilano SR, Brown DJ, Holguin B, Small K, Nesburn AB et al. SOD1: a candidate gene for keratoconus. Invest Ophthalmol Vis Sci 2006; 47: 3345–3351.
Erel O . A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37: 277–285.
Saijyothi AV, Fowjana J, Madhumathi S, Rajeshwari M, Thennarasu M, Prema P et al. Tear fluid small molecular antioxidants profiling shows lowered glutathione in keratoconus. Exp Eye Res 2012; 103: 41–46.
Balasubramanian SA, Mohan S, Pye DC, Willcox MD . Proteases, proteolysis and inflammatory molecules in the tears of people with keratoconus. Acta Ophthalmol 2012; 90: e303–e309.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
The abstract of this study was presented as poster presentation for the Congress of the European Society of Ophthalmology (SOE) 2013 (8–11 June 2013, Copenhagen, Denmark).
Rights and permissions
About this article
Cite this article
Toprak, I., Kucukatay, V., Yildirim, C. et al. Increased systemic oxidative stress in patients with keratoconus. Eye 28, 285–289 (2014). https://doi.org/10.1038/eye.2013.262
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/eye.2013.262
Keywords
This article is cited by
-
Serum inflammatory biomarkers are associated with increased choroidal thickness in keratoconus
Scientific Reports (2023)
-
Protection effect of thymosin β4 on ethanol injury in corneal stromal keratocyte
BMC Ophthalmology (2022)
-
Assessment of serum catalase, reduced glutathione, and superoxide dismutase activities and malondialdehyde levels in keratoconus patients
Eye (2022)
-
Systemic oxidative stress biomarkers in patients with vitreomacular traction syndrome
International Ophthalmology (2021)
-
Increased choroidal thickness is not a disease progression marker in keratoconus
Scientific Reports (2020)
