Oxidative Stress in Keratoconus?

Arnal, Emma; Peris-Martínez, Cristina; Menezo, J.L.; Johnsen-Soriano, Siv; Romero, Francisco J.

doi:10.1167/iovs.11-7732

Cited by 146 publications

(134 citation statements)

References 45 publications

(44 reference statements)

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“…112,113,119,120 Increasing evidence supports the fact that thinning and ectasia of the cornea are related to a degraded extracellular matrix involving inflammatory events (mainly increased levels of MMP-9, IL-6, and TNF-α) 10,[12][13][14]67,91 and increased oxidative stress. [143][144][145][146] However, the precise role of each of the identified molecular factors still needs to be defined in further studies.…”

Section: Resultsmentioning

confidence: 99%

“…19,20,106,[108][109][110]144 An important decrease in the level of protease inhibitors such as cystatins (inhibitors of cysteine proteases) and TIMP-1 (inhibitor of MMPs) have also been reported. 95,96,101,[129][130][131] The increased activity of several proteolytic enzymes results in higher concentrations of ROS, RNS, cytotoxic aldehydes (CAs) and peroxynitrates (Ps) (which decreases the activity of TIMP-1 and increase MMP-2), 63,143,144,146,149 and given the lower production of SOD 143 possibly related to IL-1α, 158 an environment with high oxidative stress and low pH is formed, causing an increase in the activation of the caspases (caspase-9 and -12), mitochondrial dysfunction (MD), and DNA damage, 156 which eventually lead to increased apoptosis. All of these could probably be the result of a complex interaction of both genetic predisposition and environmental triggering factors, such as eye rubbing and contact lenses wear (the 'two-hit hypothesis') in keratoconus.…”

Section: Resultsmentioning

confidence: 99%

“…73 Keratocytes are particularly susceptible to oxidative stress and it may have an important role in the development and progression of keratoconus. Keratoconus corneas have been shown to have a decreased glutathione content and total antioxidant capacity, 143 which can be related to increased oxidative stress that may induce oxidative damage to tissue components. 106,144 Thus, alterations of these antioxidant pathways may lead to accumulation of toxic byproducts, which eventually may induce apoptosis of the corneal cells.…”

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confidence: 99%

“…63,143,144,146 In addition, in vitro studies have shown that IL-1α, which is high in keratoconus, has the ability to decrease the synthesis of the SOD, whereby antioxidant defenses become insufficient. 147 NO is an endogenous substance, which regulates complex processes in ocular tissues.…”

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confidence: 99%

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Keratoconus: an inflammatory disorder?

Galvis

Sherwin

Tello

et al. 2015

Eye

288

199

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Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Keratoconus: an inflammatory disorder?

Galvis

Sherwin

Tello

et al. 2015

Eye

288

199

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“…In the healthy cornea, a number of defensive mechanisms such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase are present to eliminate oxidative byproducts. 4,5 However, keratoconic corneas have accumulation of cytotoxic byproducts (such as superoxides, hydrogen peroxide, and hydroxyl radicals) and abnormalities in antioxidant defense mechanisms. [6][7][8] More recently, corneal thinning in the keratoconus has been found to be associated with increase in tissue proteinase activities and decrease in proteinase inhibitor levels induced by oxidant products.…”

Section: Introductionmentioning

confidence: 99%

Increased systemic oxidative stress in patients with keratoconus

Toprak

Küçükatay

Yıldırım

et al. 2013

Eye

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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) (P40.05). The serum TOS and OSI values were significantly higher in patients with keratoconus compared with those of the controls (P ¼ 0.036 and 0.037, respectively). However, serum TAS did not show significant difference between the keratoconus and control groups (P ¼ 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.

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Genetics of Keratoconus

Chaturvedi

Hansoge

2013

Encyclopedia of Life Sciences

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Keratoconus is a mysterious disease of cornea with diverse genetic complexity. Past 160 years of molecular genetics revolution has witnessed the identification of candidate genes with multiple loci through genome‐wide association studies (GWAS). This article provides key insight into the genetics of keratoconus along with diagnosis, treatment and management. Key Concepts: Keratoconus is a noninflammatory corneal progressive ectasia that is bilateral and asymmetric, characterised by steepening and deformation of the cornea, thinning of the apical cornea and corneal scarring. Patients with moderate keratoconus are observed with Fleischer ring around the cone base due to an accumulation of iron deposits. Also Vogt striae, which are fine vertical lines due to compression of Descemet membrane, can be seen. In keratoconus, the cornea's normal defence system is lost and leads to accumulation of free radicals in the tissue, which can cause structural damage. Monozygotic twins have higher concordance of keratoconus than dizygotic twins, which is shown by their phenotypic similarity. This type of evaluation can be made in situations where a clinical sign does not show a genetic pattern. As far as the age groups that get afflicted with the disease are concerned, the keratoconus‐affected individuals between 30–40 years of age are higher than the other groups. Approximately 17 genomic loci have been described from 12 studies based on linkage analysis. This propounds at large the genetic disparities in keratoconus. Further, these studies make possible to consider the mutational effects in different genes that are responsible for the disease. Visual System Homeobox 1 ( VSX1 ) is the most widely reported gene for keratoconus. This gene codes for a transcription factor that helps in ocular development and development of cornea. Mutations in the locus of this gene are reported to be pathogenic and are positive in keratoconus patients. Early signs for diagnosing include irregularity of reflex observed by retinoscopy, distortion of the corneal reflection observed by keratometry and conical contour revealed by the fit of a corneal lens. Nowadays, surgical procedures to selectively replace either the anterior or the posterior layer are used. Keratoplasty is employed to remove the damaged cornea. The distorted cornea is replaced entirely or partially by graft. Entire removal of the keratoconic cornea is called penetrating keratoplasty, whereas if a part of the cornea is removed, it is called lamellar keratoplasty.

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Oxidative Stress in Keratoconus?

Cited by 146 publications

References 45 publications

Keratoconus: an inflammatory disorder?

Keratoconus: an inflammatory disorder?

Increased systemic oxidative stress in patients with keratoconus

Genetics of Keratoconus

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