The impairment of lysyl oxidase in keratoconus and in keratoconus-associated disorders

Ďuďáková, Ľubica; Jirsová, Kateřina

doi:10.1007/s00702-013-0993-1

Cited by 34 publications

(29 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dudakova and Jirsova hypothesized that very similar changes in the extracellular matrix, particularly at the level of collagen metabolism, including lysyl oxidase (LOX) impairment in mitral leaflets, may reflect an association between KC and mitral valve prolapse. As such, these findings may also indicate a very similar origin of KC and MVP [33]. …”

Section: Discussionmentioning

confidence: 94%

Impaired Corneal Biomechanical Properties and the Prevalence of Keratoconus in Mitral Valve Prolapse

Akçay

Uysal

et al. 2014

Journal of Ophthalmology

View full text Add to dashboard Cite

Objective. To investigate the biomechanical characteristics of the cornea in patients with mitral valve prolapse (MVP) and the prevalence of keratoconus (KC) in MVP. Materials and Methods. Fifty-two patients with MVP, 39 patients with KC, and 45 control individuals were recruited in this study. All the participants underwent ophthalmologic examination, corneal analysis with the Sirius system (CSO), and the corneal biomechanical evaluation with Reichert ocular response analyzer (ORA). Results. KC was found in six eyes of four patients (5.7%) and suspect KC in eight eyes of five patients (7.7%) in the MVP group. KC was found in one eye of one patient (1.1%) in the control group (P = 0.035). A significant difference occurred in the mean CH and CRF between the MVP and control groups (P = 0.006 and P = 0.009, resp.). All corneal biomechanical and topographical parameters except IOPcc were significantly different between the KC-MVP groups (P < 0.05). Conclusions. KC prevalence is higher than control individuals in MVP patients and the biomechanical properties of the cornea are altered in patients with MVP. These findings should be considered when the MVP patients are evaluated before refractive surgery.

show abstract

Section: Discussionmentioning

confidence: 94%

Impaired Corneal Biomechanical Properties and the Prevalence of Keratoconus in Mitral Valve Prolapse

Akçay

Uysal

et al. 2014

Journal of Ophthalmology

View full text Add to dashboard Cite

show abstract

“…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

275

199

View full text Add to dashboard Cite

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.

show abstract

“…[21] Reduced LOX activity has been detected in the cornea of patients with KC, suggesting a significant role of this gene in the pathogenesis of disease. [15,22,23] Two of the main missense mutations, Arg158Gln (rs1800449) and Pro159Gln (rs41407546), have been described in both Italian and Iranian populations [16,20] . A role of the Arg158Gln mutation in KC has been demonstrated in a genome-wide association study that also identified an SNP associated with the 5'UTR region.…”

Section: Introductionmentioning

confidence: 99%

Screening for Novel LOX and SOD1 Variants in Keratoconus Patients from Brazil

Gadelha¹,

Feitosa²,

Silva³

et al. 2020

JOVR

View full text Add to dashboard Cite

Purpose: To investigate the presence of the variants of lysyl oxygenase (LOX) and superoxide dismutase 1 (SOD1) genes in Brazilian patients with advanced keratoconus. Methods: Donor genomic DNA extracted from blood samples was screened for 5’UTR, exonic LOX, and SOD1 variants in a subset of 26 patients presenting with advanced keratoconus (KISA > 1000% and I–S > 2.0) by Sanger sequencing. The impact of non-synonymous amino acid changes was evaluated by SIFT, PMUT, and PolyPhen algorithms. The Mutation Taster tool was used to evaluate the potential impact of formation of new donor and acceptor splice sites in the promoter region of affected volunteers carrying sequence variants. A 7-base SOD1 deletion (IVS2 + 50del7bp) previously associated with keratoconus was screened in 140 patients presenting classical keratoconus by gel fragment analysis, and positive samples were sequenced for confirmation. Results: We found an unreported missense variant in LOX exon 6 in one heterozygous patient, leading to substitution of proline with threonine at residue 392 (p. Thr392Pro) of LOX protein sequence. This mutation was predicted to be potentially damaging to LOX protein. Another LOX variant, Arg158Gln, was also detected in another patient but predicted to be non-pathogenic. Two additional new polymorphisms in LOX 5’UTR region (–116C > T and –58C > T) were found in two patients presenting with advanced keratoconus and were predicted to modulate or create donor/acceptor splice sites in LOX transcripts. Additionally, SOD1 deletion was detected in one patient presenting with severe keratoconus, not in control samples. Conclusion: We described three novel LOX polymorphisms identified for the first time in Brazilian patients with advanced keratoconus, as well as a previously described SOD1 deletion strongly associated with keratoconus. A possible role of these variants in modulating transcript levels in the cornea of affected individual requires further investigation.

show abstract

The impairment of lysyl oxidase in keratoconus and in keratoconus-associated disorders

Cited by 34 publications

References 63 publications

Impaired Corneal Biomechanical Properties and the Prevalence of Keratoconus in Mitral Valve Prolapse

Impaired Corneal Biomechanical Properties and the Prevalence of Keratoconus in Mitral Valve Prolapse

Keratoconus: an inflammatory disorder?

Screening for Novel LOX and SOD1 Variants in Keratoconus Patients from Brazil

Contact Info

Product

Resources

About