Lamellar changes in the keratoconic cornea

Mathew, Jessica H.; Goosey, John D.; Söderberg, Per G.; Bergmanson, Jan P.G.

doi:10.1111/aos.12811

Cited by 35 publications

(26 citation statements)

References 27 publications

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“…The latest ultrastructural analysis of keratoconic corneal buttons, using transmission electron microscopy, suggested that KTCN is associated with the splitting of existing collagen lamellae into smaller units, which results in a higher total lamellar count. 37 The mechanism of lamellar alteration in KTCN stroma is not fully understood. However, several studies have indicated that collagen slippage observed in KTCN corneas may be due to a loss of cohesion between collagen fibrils and other ECM components.…”

Section: Discussionmentioning

confidence: 99%

Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas

et al. 2017

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To understand better the factors contributing to keratoconus (KTCN), we performed comprehensive transcriptome profiling of human KTCN corneas for the first time using an RNA-Seq approach. Twenty-five KTCN and 25 non-KTCN corneas were enrolled in this study. After RNA extraction, total RNA libraries were prepared and sequenced. The discovery RNA-Seq analysis (in eight KTCN and eight non-KTCN corneas) was conducted first, after which the replication RNA-Seq experiment was performed on a second set of samples (17 KTCN and 17 non-KTCN corneas). Over 82% of the genes and almost 75% of the transcripts detected as differentially expressed in KTCN and non-KTCN corneas were confirmed in the replication study using another set of samples. We used these differentially expressed genes to generate a network of KTCN-deregulated genes. We found an extensive disruption of collagen synthesis and maturation pathways, as well as downregulation of the core elements of the TGF-β, Hippo, and Wnt signaling pathways influencing corneal organization. This first comprehensive transcriptome profiling of human KTCN corneas points further to a complex etiology of KTCN.

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Section: Discussionmentioning

confidence: 99%

Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas

et al. 2017

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“…Several studies suggest that thinning of the KC cornea might be occurring due to a defect of collagen lamellae formation (Chen et al, 2015; Mathew et al, 2015; White et al, 2017). The different distribution of stromal lamellae in KC compared to normal corneas has been suggested as a precursor for corneal thinning and KC development (Khaled et al, 2017).…”

Section: Pathobiology Of Keratoconusmentioning

confidence: 99%

Pathogenesis of Keratoconus: The intriguing therapeutic potential of Prolactin-inducible protein

Sharif

Bak‐Nielsen

Hjortdal

et al. 2018

Progress in Retinal and Eye Research

103

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Keratoconus (KC) is the most common ectatic corneal disease, with clinical findings that include discomfort, visual disturbance and possible blindness if left untreated. KC affects approximately 1:400 to 1:2000 people worldwide, including both males and females. The aetiology and onset of KC remains a puzzle and as a result, the ability to treat or reverse the disease is hampered. Sex hormones are known to play a role in the maintenance of the structure and integrity of the human cornea. Hormone levels have been reported to alter corneal thickness, curvature, and sensitivity during different times of menstrual cycle. Surprisingly, the role of sex hormones in corneal diseases and KC has been largely neglected. Prolactin-induced protein, known to be regulated by sex hormones, is a new KC biomarker that has been recently proposed. Studies herein discuss the role of sex hormones as a control mechanism for KC onset and progression and evidence supporting the view that prolactin-induced protein is an important hormonally regulated biomarker in KC is discussed.

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“…In the normal cornea, the anterior stroma is believed to be biomechanically stronger than the posterior stroma due to a high degree of lamellar interweaving (Komai and Ushiki, 1991, Morishige et al., 2006); however, numerous studies have shown that lamellar interweaving is significantly reduced in the anterior stroma of keratoconus corneas, as well as a loss of collagen lamellae inserting into Bowman's layer (Mathew et al., 2015, Morishige et al., 2007, Morishige et al., 2014, Radner et al., 1998a), ultimately facilitating lamellar “slippage” (Meek et al., 2005). The central anterior cornea is a weak area in keratoconus, forming the apex of the cone, and likely in need of additional biomechanical strength to that provided by collagen.…”

Section: Discussionmentioning

confidence: 99%

Elastic microfibril distribution in the cornea: Differences between normal and keratoconic stroma

White

Lewis

Young

et al. 2017

Experimental Eye Research

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The optical and biomechanical properties of the cornea are largely governed by the collagen-rich stroma, a layer that represents approximately 90% of the total thickness. Within the stroma, the specific arrangement of superimposed lamellae provides the tissue with tensile strength, whilst the spatial arrangement of individual collagen fibrils within the lamellae confers transparency. In keratoconus, this precise stromal arrangement is lost, resulting in ectasia and visual impairment. In the normal cornea, we previously characterised the three-dimensional arrangement of an elastic fiber network spanning the posterior stroma from limbus-to-limbus. In the peripheral cornea/limbus there are elastin-containing sheets or broad fibers, most of which become microfibril bundles (MBs) with little or no elastin component when reaching the central cornea. The purpose of the current study was to compare this network with the elastic fiber distribution in post-surgical keratoconic corneal buttons, using serial block face scanning electron microscopy and transmission electron microscopy.We have demonstrated that the MB distribution is very different in keratoconus. MBs are absent from a region of stroma anterior to Descemet's membrane, an area that is densely populated in normal cornea, whilst being concentrated below the epithelium, an area in which they are absent in normal cornea. We contend that these latter microfibrils are produced as a biomechanical response to provide additional strength to the anterior stroma in order to prevent tissue rupture at the apex of the cone. A lack of MBs anterior to Descemet's membrane in keratoconus would alter the biomechanical properties of the tissue, potentially contributing to the pathogenesis of the disease.

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Lamellar changes in the keratoconic cornea

Cited by 35 publications

References 27 publications

Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas

Collagen synthesis disruption and downregulation of core elements of TGF-β, Hippo, and Wnt pathways in keratoconus corneas

Pathogenesis of Keratoconus: The intriguing therapeutic potential of Prolactin-inducible protein

Elastic microfibril distribution in the cornea: Differences between normal and keratoconic stroma

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