A comparative study of the elastic fibre system within the mouse and human cornea

Feneck, Eleanor M.; Lewis, Philip N.; Ralphs, J. R.; Meek, Keith Michael Andrew

doi:10.1016/j.exer.2018.07.024

Cited by 22 publications

(18 citation statements)

References 36 publications

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“…This technique is believed to be specific for elastic fiber enhancement, and this was confirmed in our previous publication using antibody staining specific to elastin and fibrillin-1. 32 Our results showed that elastic fibers are present from week 12 of fetal development and are confined to the posterior corneal stroma.…”

Section: Discussionsupporting

confidence: 53%

“…The tannic acid–uranyl acetate method has been previously described in numerous studies to enhance the contrast for elastic fibers within the cornea. 18 - 20 , 31 , 32 The elastic fibers were imaged as bundles of fibrillin-rich microfibrils, with some fibers containing an elastin core, characteristic of true elastic fibers, as described by previous studies. 18 The elastic fibers were initially identified from week 12 of corneal development as small and round bundles of microfibrils concentrated within the posterior peripheral region of the cornea.…”

Section: Discussionmentioning

confidence: 99%

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Identification of a Primary Stroma and Novel Endothelial Cell Projections in the Developing Human Cornea

Feneck

Lewis

Meek

2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To investigate the initial events in the development of the human cornea, focusing on cell migration, and extracellular matrix synthesis and organization. To determine whether elastic fibers are present in the extracellular matrix during early human corneal development. METHODS. Human corneas were collected from week 7 to week 17 of development. An elastic fiber-enhancing stain, tannic acid-uranyl acetate, was applied to all tissue. Threedimensional serial block-face scanning electron microscopy combined with conventional transmission electron microscopy was used to analyze the corneal stroma. RESULTS. An acellular collagenous primary stroma with an orthogonal arrangement of fibrils was identified in the central cornea from week 7 of corneal development. At week 7.5, mesenchymal cells migrated toward the central cornea and associated with the acellular collagenous matrix. Novel cell extensions from the endothelium were identified. Elastic fibers were found concentrated in the posterior peripheral corneal stroma from week 12 of corneal development. CONCLUSIONS. This study provides novel evidence of an acellular primary stroma in the early development of the embryonic human cornea. Cell extensions exist as part of a communication system and are hypothesized to assist in the migration of the mesenchymal cells and the development of the mature cornea. Elastic fibers identified in early corneal development may play an important role in establishing corneal shape.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Identification of a Primary Stroma and Novel Endothelial Cell Projections in the Developing Human Cornea

Feneck

Lewis

Meek

2020

Invest. Ophthalmol. Vis. Sci.

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“…Finally, we observed reduced expression of collagen-VI, which is constitutively expressed in the corneal stroma 90 . Reduction in COLVI could promote CNV by altering the corneal biomechanics.…”

Section: Discussionmentioning

confidence: 65%

The role of extracellular matrix in mouse and human corneal neovascularization

Barbariga

Vallone

Mosca

et al. 2019

Sci Rep

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Corneal neo-vascularization (CNV) is a highly prevalent medical condition which impairs visual acuity. The role of specific proteins in modulating CNV has been extensively reported, although no studies have described the entire human proteome in CNV corneas. In this paper, we performed a proteomic analysis of vascularized vs healthy corneal stroma, in a CNV mouse model and in CNV-affected patients, with a specific focus on extracellular matrix (ECM) proteins. We identified and quantified 2315 murine proteins, 691 human proteins and validated 5 proteins which are differentially expressed in vascularized samples and conserved in mice and humans: tenascin-C and fibronectin-1 were upregulated, while decorin, lumican and collagen-VI were downregulated in CNV samples. Interestingly, among CNV patients, those affected with Acanthamoeba keratitis showed the highest levels of fibronectin-1 and tenascin-C, suggesting a specific role of these two proteins in Acanthamoeba driven corneal CNV. On a broader picture, our findings support the hypothesis that the corneal stroma in CNV samples is disorganized and less compact. We are confident that the dissection of the human corneal proteome may shed new light on the complex pathophysiology of human CNV, and finally lead to improved treatments.

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“…As is well known, the human cornea is rich in extracellular matrix (ECM), which maintains corneal transparency and biomechanical strength [12]. Through medical biochemistry techniques-such as immunostaining technology-and proteomics, different abnormalities related to varying risk genes in the expression of ECM components were identi ed in KC patients [13].…”

Section: Genementioning

confidence: 99%

Novel mutations identified in the Chinese Han population with keratoconus by next-generation sequencing

Chen

Zhang

et al. 2020

Preprint

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BACKGROUND Keratoconus (KC) is characterized by bilateral progressive corneal thinning and ectasia. The prevalence of KC is approximately 8.8 to 54.4 per 100,000 individuals across the globe. Genetic factors have been shown to contribute to the pathogenesis of KC. This study will identify new mutations in the susceptibility gene of keratoconus (KC) in the Chinese Han population. METHODS A total of fifty-two patients with primary KC were recruited. Blood samples were collected, and genomic DNA was isolated from peripheral blood leukocytes. The entire coding region, intron–exon junctions, and promoter regions of sixteen known KC susceptibility genes were screened with next-generation sequencing technology, and all identified variants were further confirmed using the Sanger sequencing technology. The Sorting Intolerant from Tolerant (SIFT), Mutation Taster and PolyPhen 2 programs were used to predict the effect of amino acid substitution on protein. RESULTS After removing twelve known SNPs (single nucleotide polymorphisms) and three variants predicted to be harmless, nine novel mutations were identified in eight of the fifty-two patients, including c.455C > T:p.P152L in FNDC3B, c.3636_3637del:p.R1212fs in COL4A4, c.5015G > T:p.R1672L, c.3798dupA:p.P1267fs and c.28G > A:p.A10T in MPDZ, c.1940C > T:p.P647L in DOCK9, c.127_128insGGC:p.Q43delinsRQ in POLG, c.3019G > A:p.V1007I in IPO5, and c.624 + 7->A in TGFBI. All nine mutations in the patients with KC were heterozygote. CONCLUSION This study enlarged the gene profile of KC and should be further confirmed by well-powered, genome-wide association studies (GWAS) of Han Chinese patients.

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A comparative study of the elastic fibre system within the mouse and human cornea

Cited by 22 publications

References 36 publications

Identification of a Primary Stroma and Novel Endothelial Cell Projections in the Developing Human Cornea

Identification of a Primary Stroma and Novel Endothelial Cell Projections in the Developing Human Cornea

The role of extracellular matrix in mouse and human corneal neovascularization

Novel mutations identified in the Chinese Han population with keratoconus by next-generation sequencing

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