Collagens and proteoglycans of the cornea: importance in transparency and visual disorders

Massoudi, Dawiyat; Malecaze, F; Galiacy, Stéphane

doi:10.1007/s00441-015-2233-5

Cited by 86 publications

(67 citation statements)

References 122 publications

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“…38 In addition to collagens, other ECM molecules, including proteoglycans, have a role in fibrillogenesis and matrix assembly in human corneas. 39 Recently, it was shown that one of the major corneal proteoglycans, LUM -encoding lumican, was downregulated in cell cultures derived from KTCN corneas and in the corneas. 34,40 In this study, the expression of LUM, was also diminished, which could destabilize normal corneal fibril organization.…”

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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“…The beaded intermediate filaments (CP49 and filensin) have the outer diameter about 10–18 nm [Quinlan et al,1999], with some smaller nanoparticles organized around the filaments, being very important intermediate filaments in the eye lens fiber cells, determining their transparency [Tagliavini et al, 1986; Bloemendal, 1991; Marcantonio, Duncan, 1991; Rafferty et al, 1997; Matsushima et al, 1997; Clark et al, 1999; Alizadeh et al, 2002, 2003, 2004; Oka et al, 2008; Song et al, 2009]. Similarly, the transparency of the corneal cells also depends on the specialized collagen filaments [Jester, 2008; Massoudi et al, 2015]. …”

Section: Discussionmentioning

confidence: 99%

Foveolar Müller Cells of the Pied Flycatcher: Morphology and Distribution of Intermediate Filaments Regarding Cell Transparency

et al. 2016

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The specialized intermediate filaments (IFs) have critical importance for the clearness and uncommon transparency of the vertebrates' lens fiber cells, although the physical mechanisms involved are poorly understood. Recently, an unusual low-scattering light transport was also described in the retinal Müller cells. Exploring the function of the IFs in the Müller cells, we have studied the morphology and distribution pattern of the IFs and other cytoskeletal filaments inside the Müller cell main processes in the foveolar part of the avian (Pied Flycatcher) retina. We found that some IFs surrounded by globular nanoparticles (that we suggest are crystallines) are present in almost every part of the Müller cells that span the retina, including the microvilli. Unlike the IFs implicated in the mechanical architecture of the cell, these IFs are not connected to any specific cellular membranes. Instead, they are organized into bundles, passing inside the cell from the endfeet to the photoreceptor, following the geometry of the processes and repeatedly circumventing numerous obstacles. We believe that all of the presently reported data effectively confirms that the model of nanooptical channels built of the intermediate filaments [Makarov et al., 2015, Khmelinskii et al., 2015] may provide a viable explanation of the Müller cell transparency.

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“…22,23 Collagenase has thus been implicated in corneal destruction after alkali-induced burn or other injury. [24][25][26] The expression of collagenase (MMP-1) has been found to be increased in association with destructive corneal disease.…”

Section: Discussionmentioning

confidence: 99%

Suppression by an RAR-γ Agonist of Collagen Degradation Mediated by Corneal Fibroblasts

Kimura

Zhou

Orita

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To examine the role of retinoic acid receptor (RAR) isoforms in interleukin-1b (IL1b)-induced collagen degradation by corneal fibroblasts.METHODS. Primary rabbit corneal fibroblasts embedded in a three-dimensional collagen gel were incubated with or without all-trans retinoic acid (ATRA), the RAR-a agonist Am580, the RAR-b agonist AC55649, or the RAR-c agonist R667. Collagen degradation was determined by measurement of hydroxyproline produced in acid hydrolysates of culture supernatants. Matrix metalloproteinase (MMP) expression was evaluated by immunoblot analysis and gelatin zymography. The phosphorylation of mitogen-activated protein kinases (MAPKs) and the endogenous nuclear factor (NF)-jB inhibitor IjB-a was examined by immunoblot analysis. Cell proliferation was measured with a bromodeoxyuridine incorporation assay, and cell viability was determined by measurement of the release of lactate dehydrogenase. RESULTS.Interleukin-1b-induced collagen degradation by corneal fibroblasts was inhibited by ATRA, Am580, and R667 in a concentration-dependent manner but was unaffected by AC55649, with the inhibitory effects of ATRA and R667 being markedly greater than that of Am580. The IL-1b-induced production of MMP-1, MMP-2, MMP-3, and MMP-9 by corneal fibroblasts was also inhibited by R667 in a concentration-dependent manner. R667 inhibited the IL-1b-induced phosphorylation of IjB-a but not that of MAPKs. R667 had no effect on the proliferation or viability of corneal fibroblasts.CONCLUSIONS. The RAR-c agonist R667 suppressed MMP production and thereby inhibited collagen degradation by corneal fibroblasts exposed to the proinflammatory cytokine IL-1b. These effects of R667 may be mediated by the NF-jB signaling pathway.

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Collagens and proteoglycans of the cornea: importance in transparency and visual disorders

Cited by 86 publications

References 122 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

Foveolar Müller Cells of the Pied Flycatcher: Morphology and Distribution of Intermediate Filaments Regarding Cell Transparency

Suppression by an RAR-γ Agonist of Collagen Degradation Mediated by Corneal Fibroblasts

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