Changes in lysyl oxidase (LOX) distribution and its decreased activity in keratoconus corneas

Ďuďáková, Ľubica; Lišková, Petra; Trojek, T.; Palos, Michalis; Kalasova, Sarka; Jirsová, Kateřina

doi:10.1016/j.exer.2012.09.005

Cited by 92 publications

(68 citation statements)

References 45 publications

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“…Although the underlying mechanism of common variants contributing to the disease development remains unknown, the potential effect could lie in affecting the biologic activity of LOX via tissue specific alternative splicing or regulation of expression. 14 Mechanisms of how common variants within the HGF gene alter susceptibility to KC are yet to be determined, but involvement of inflammatory pathways has been previously suggested. 8 The main statistics used here (allelic test) implicitly assume codominance, and is similar to the additive models assumed in the previous reports.…”

Section: Discussionmentioning

confidence: 99%

Validation of rs2956540:G>C and rs3735520:G>A association with keratoconus in a population of European descent

et al. 2015

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Corneal ectasias, among which keratoconus (KC) is the single most common entity, are one of the most frequent reasons for corneal grafting in developed countries and a threatening complication of laser in situ keratomileusis. Genome-wide association studies have previously found lysyl oxidase (LOX) and hepatocyte growth factor (HGF) associated with susceptibility to KC development. The aim of our study was to validate the effects of seven single-nucleotide polymorphisms (SNPs) within LOX and HGF over KC. Unrelated Czech cases with KC of European descent (108 males and 57 females, 165 cases in total) and 193 population and gender-matched controls were genotyped using Kompetitive Allele Specific PCR assays. Fisher's exact tests were used to assess the strength of associations. Evidence for association was found for both of the tested loci. It was strongest for rs3735520:G4A near HGF (allelic test odds ratio (OR) = 1.45; 95% confidence interval (CI), 1.06-1.98; P = 0.018) with A allele being a risk factor and rs2956540:G4C (OR = 0.69; 95% CI, 0.50-0.96; P = 0.024) within LOX with C allele having a protective effect. This first independent association validation of rs2956540:G4C and rs3735520:G4A suggests that these SNPs may serve as genetic risk markers for KC in individuals of European descent.

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Section: Discussionmentioning

confidence: 99%

Validation of rs2956540:G>C and rs3735520:G>A association with keratoconus in a population of European descent

et al. 2015

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“…137,138 In 63% of cases of keratoconus, LOX distribution has been found to be markedly decreased and its activity to be more than 2.5 times lower than that of control cases. 139,140 A study in Russia has shown that the increase in pH of the tears causes biochemical changes in the periphery of the cornea that prevent the passage of Keratoconus IL-1α, interleukin 1α; KC, keratoconous; β-NGF, nerve growth factor-β; PDGF, platelet-derived growth factor; PGE2, prostaglandin E2; PIGR, polymeric immunoglobulin receptor; RGP, rigid gas permeable; TGF-β1, transforming growth factor β1;…”

Section: Enzymatic Imbalancementioning

confidence: 99%

Keratoconus: an inflammatory disorder?

Galvis

Sherwin

Tello

et al. 2015

Eye

303

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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“…KCN may involve a disturbance of the balance between proteolytic breakdown and repair [18]. Both the concentration and the activity of the crosslinking enzyme lysyl oxidase have been shown to be significantly reduced in KCN corneas [19]. Mechanically, the KCN cornea shows a substantial reduction in stiffness [20].…”

Section: Corneal Biomechanical Propertiesmentioning

confidence: 99%

Corneal Collagen Crosslinking: A Systematic Review

Sorkin

Varssano²

2014

Ophthalmologica

166

122

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Keratoconus (KCN) is an ectatic disorder with progressive corneal thinning and a clinical picture of corneal protrusion, progressive irregular astigmatism, corneal fibrosis and visual deterioration. Other ectatic corneal disorders include: post-LASIK ectasia (PLE) and pellucid marginal degeneration (PMD). Corneal crosslinking (CXL) is a procedure whereby riboflavin sensitization with ultraviolet A radiation induces stromal crosslinks. This alters corneal biomechanics, causing an increase in corneal stiffness. In recent years, CXL has been an established treatment for the arrest of KCN, PLE and PMD progression. CXL has also been shown to be effective in the treatment of corneal infections, chemical burns, bullous keratopathy and other forms of corneal edema. This is a current review of CXL - its biomechanical principles, the evolution of CXL protocols in the past, present and future, indications for treatment, treatment efficacy and safety.

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Changes in lysyl oxidase (LOX) distribution and its decreased activity in keratoconus corneas

Cited by 92 publications

References 45 publications

Validation of rs2956540:G>C and rs3735520:G>A association with keratoconus in a population of European descent

Validation of rs2956540:G>C and rs3735520:G>A association with keratoconus in a population of European descent

Keratoconus: an inflammatory disorder?

Corneal Collagen Crosslinking: A Systematic Review

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