Genetic and Environmental Risk Factors for Keratoconus

Lucas, Sionne E. M.; Burdon, Kathryn P.

doi:10.1146/annurev-vision-121219-081723

Cited by 64 publications

(46 citation statements)

References 114 publications

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“…Because of the complex etiology and the genetic heterogeneity of the disease, the identification of specific risk factors for KTCN is difficult. However, the use of various approaches has already allowed detection of many candidate genes that could be implicated in KTCN as have been previously reviewed ( Nowak & Gajecka, 2011 ; Abu-Amero, Al-Muammar & Kondkar, 2014 ; Bykhovskaya, Margines & Rabinowitz, 2016 ; Karolak & Gajecka, 2017 ; Valgaeren, Koppen & Van Camp, 2018 ; Loukovitis et al, 2018 ; Lucas & Burdon, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Further evaluation of differential expression of keratoconus candidate genes in human corneas

Karolak

Ginter-Matuszewska

Tomela

et al. 2020

PeerJ

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Background Keratoconus (KTCN) is a progressive eye disease, characterized by changes in the shape and thickness of the cornea that results in loss of visual acuity. While numerous KTCN candidate genes have been identified, the genetic etiology of the disease remains undetermined. To further investigate and verify the contribution of particular genetic factors to KTCN, we assessed 45 candidate genes previously indicated as involved in KTCN etiology based on transcriptomic and genomic data. Methods The RealTime ready Custom Panel, covering 45 KTCN candidate genes and two reference transcripts, has been designed. Then, the expression profiles have been assessed using the RT-qPCR assay in six KTCN and six non-KTCN human corneas, obtained from individuals undergoing a penetrating keratoplasty procedure. Results In total, 35 genes exhibiting differential expression between KTCN and non-KTCN corneas have been identified. Among these genes were ones linked to the extracellular matrix formation, including collagen synthesis or the TGF-β, Hippo, and Wnt signaling pathways. The most downregulated transcripts in KTCN corneas were CTGF, TGFB3, ZNF469, COL5A2, SMAD7, and SPARC, while TGFBI and SLC4A11 were the most upregulated ones. Hierarchical clustering of expression profiles demonstrated almost clear separation between KTCN and non-KTCN corneas. The gene expression levels determined using RT-qPCR showed a strong correlation with previous RNA sequencing (RNA-Seq) results. Conclusions A strong correlation between RT-qPCR and earlier RNA-Seq data confirms the possible involvement of genes from collagen synthesis and the TGF-β, Hippo, and Wnt signaling pathways in KTCN etiology. Our data also revealed altered expression of several genes, such as LOX, SPARC, and ZNF469, in which single nucleotide variants have been frequently identified in KTCN. These findings further highlight the heterogeneous nature of KTCN.

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Section: Introductionmentioning

confidence: 99%

Further evaluation of differential expression of keratoconus candidate genes in human corneas

Karolak

Ginter-Matuszewska

Tomela

et al. 2020

PeerJ

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“…[20][21][22] This gene encodes a cytoplasmic enzyme that detoxi es superoxide radicals, a form of reactive oxygen species, and thus reduces the level of oxidative stress in cells. 20 Increased levels of oxidative stress in corneal cells appear to be a predisposing factor for KC, so it has been proposed that a mutation in SOD1 increases oxidative stress and is involved in the pathogenesis of ectatic disorders. 20 Nevertheless, there is no consensus on the role of SOD1 in KC, and there are different pieces of evidence about it.…”

Section: Discussionmentioning

confidence: 99%

“…20 Increased levels of oxidative stress in corneal cells appear to be a predisposing factor for KC, so it has been proposed that a mutation in SOD1 increases oxidative stress and is involved in the pathogenesis of ectatic disorders. 20 Nevertheless, there is no consensus on the role of SOD1 in KC, and there are different pieces of evidence about it. 19,20 SOD1 is the only candidate gene for KC located on chromosome 21, and it could explain the association between KC and DS in some way.…”

Section: Discussionmentioning

confidence: 99%

Corneal Ectasia in Mothers of Down Syndrome Children

Hashemi

Asgari

Panahi

et al. 2021

Preprint

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In this study, corneal findings regarding keratoconus (KC) and early KC among mothers with Down syndrome children (MDS) and a group of age-at-delivery-matched mothers with normal children (MNC) were compared. KC was diagnosed based on the presence of a clinical sign and at least one abnormal tomographic or biomechanical criterion. Early KC was defined as having no clinical sign in the presence of at least one abnormal tomographic or biomechanical criterion. The normal subgroups in each group were compared in terms tomographic and biomechanical parameters. In MDS and MNC, the prevalence rates were 6.5% and 1.6% for KC (P = 0.047), and 30.9% and 14.3% for early KC (P = 0.014), respectively. Comparison between the two normal subgroups showed significant differences in mean index of height asymmetry, irregularity index, anterior asphericity, pentacam random forest index, corneal stiffness parameters at first applanation, deformation amplitude ratios, integrated radius-1mm, highest concavity deflection amplitude, biomechanical corrected IOP, peak distance, and radius (all P < 0.05). This study showed that MDS are more likely to have KC and also to have thinner, steeper and softer corneas compared to MNC. This results support the need for further work for determining the risk of delivering a child with DS.

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“…It is characterized by progressive corneal thinning and steepening [ 3 ]. Several environmental and genetic risk factors for keratoconus have been identified [ 4 , 5 ]. These risk factors are not limited to eye rubbing, dry eye, male sex, and screen time [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Environmental Risk Factors Associated With the Need for Penetrating Keratoplasty in Patients With Keratoconus

Elubous¹,

Bdour²,

Alshammari³

et al. 2021

Cureus

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To identify environmental risk factors associated with the need for penetrating keratoplasty (PKP) (fullthickness corneal transplantation) in patients with keratoconus in a Middle Eastern country. MethodsThis is a retrospective case-control study. This study included patients with keratoconus who underwent PKPor were waitlisted for PKP. Controls were patients diagnosed with keratoconus who did not reach a stage that necessitates PKP. Groups were matched by age and gender. Chi-square test was used to figure out the association between different risk factors including eye rubbing, vernal keratoconjunctivitis (VKC), smoking, paternal consanguinity, eye dryness, family history, asthma, eczema, and diabetes with the need for PKP. ResultsA total of 111 patients were included in this study, there were 48 (43.26%) men and 63 (56.75%) women. The case group included 42 subjects and the control group included 69 subjects. We found statistically significant differences between the two groups in relation to eye rubbing (p=0.0005), VKC (p=0.005), paternal consanguinity (p=0.02), and smoking rate (p=0.04), all being significant in the group in need of PKP. On the other hand, we did not find out a statistically significant difference between the two groups in relation to family history (p=0.31), dryness (p=0.58), asthma (p=0.15), eczema (p=0.28), or diabetes (p=0.29). ConclusionThis study has identified several risk factors associated with the need for PKP in patients with keratoconus, part of which are modifiable. These findings can benefit clinicians in community counseling and give recommendations that can help in preventing or -at least -delaying the need for PKP surgery in keratoconus, such as smoking cessation, aggressive treatment of VKC disease, eye rubbing avoidance, as well as raising awareness regarding the potential risks of paternal consanguinity in this disease entity.

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Genetic and Environmental Risk Factors for Keratoconus

Cited by 64 publications

References 114 publications

Further evaluation of differential expression of keratoconus candidate genes in human corneas

Further evaluation of differential expression of keratoconus candidate genes in human corneas

Corneal Ectasia in Mothers of Down Syndrome Children

Environmental Risk Factors Associated With the Need for Penetrating Keratoplasty in Patients With Keratoconus

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