Endothelial Cell MicroRNA Expression in Human Late-Onset Fuchs' Dystrophy

Matthaei, Mario; Hu, Jianfei; Kallay, Laura; Eberhart, Charles G.; Cursiefen, Claus; Jiang, Qian; Lackner, Eva; Jun, Albert S.

doi:10.1167/iovs.13-12689

Cited by 58 publications

(63 citation statements)

References 50 publications

(64 reference statements)

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“…However, in many patients the inflammation does not resolve completely, and this culminates in corneal opacification and loss of vision. 38 Recent reports on altered miRNA expression in human corneal diseases [10][11][12] suggest their regulatory role in pathogenesis. However, the miRNA expression profile in fungal keratitis has not yet been studied.…”

Section: Discussionmentioning

confidence: 99%

“…7 MicroRNAs are expressed in various ocular tissues with a distinct tissue-specific and developmental stage-specific expression pattern, which suggests potential unique functions. 8 They have also been detected in ocular fluids 9 and have been implicated in human corneal diseases like keratoconus, 10 Fuchs' dystrophy, 11 and herpetic stromal keratitis. 12 Corneal inflammation in fungal keratitis poses a significant therapeutic challenge to clinicians, particularly because of the controversial role of corticosteroids in the initial disease management.…”

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confidence: 99%

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Human Corneal MicroRNA Expression Profile in Fungal Keratitis

Hemadevi

Mohankumar

Lalitha

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. MicroRNAs (miRNAs) are small, stable, noncoding RNA molecules with regulatory function and marked tissue specificity that posttranscriptionally regulate gene expression. However, their role in fungal keratitis remains unknown. The purpose of this study was to identify the miRNA profile and its regulatory role in fungal keratitis. METHODS.Normal donor (n ¼ 3) and fungal keratitis (n ¼ 5) corneas were pooled separately, and small RNA deep sequencing was performed using a sequencing platform. A bioinformatics approach was applied to identify differentially-expressed miRNAs and their targets, and select miRNAs were validated by real-time quantitative PCR (qPCR). The regulatory functions of miRNAs were predicted by combining miRNA target genes and pathway analysis. The mRNA expression levels of select target genes were further analyzed by qPCR.RESULTS. By deep sequencing, 75 miRNAs were identified as differentially expressed with fold change greater than 2 and probability score greater than 0.9 in fungal keratitis corneas. The highly dysregulated miRNAs (miR-511-5p, miR-142-3p, miR-155-5p, and miR-451a) may regulate wound healing as they were predicted to specifically target wound inflammatory genes. Moreover, the increased expression of miR-451a in keratitis correlated with reduced expression of its target, macrophage migration inhibitory factor, suggesting possible regulatory functions.CONCLUSIONS. This is, to our knowledge, the first report on comprehensive human corneal miRNA expression profile in fungal keratitis. Several miRNAs with high expression in fungal keratitis point toward their potential role in regulation of pathogenesis. Further insights in understanding their role in corneal wound inflammation may help design new therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Human Corneal MicroRNA Expression Profile in Fungal Keratitis

Hemadevi

Mohankumar

Lalitha

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…67 Evidence of downregulation of three miR-29 family members (miR-29a-3p, miR-29b-2-5p, and miR-29c-5p) is further supported by upregulation of collagen I and collagen IV, mRNA targets which are associated with extracellular matrix production, and increased endothelial laminin protein expression FCD. 67 …”

Section: Micrornamentioning

confidence: 96%

Fuchs Corneal Dystrophy

Eghrari

Riazuddin

Gottsch

2015

Progress in Molecular Biology and Translational Science

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“…(Matthaei et al, 2013a) The experimental data were grouped into files from diseased (FECD) and normal biological replicates using the normal group as reference. A cycle threshold (Ct) value of 40 was set for detectable RNA expression.…”

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Transcript profile of cellular senescence-related genes in Fuchs endothelial corneal dystrophy

Matthaei

Zhu

Kallay

et al. 2014

Experimental Eye Research

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Fuchs endothelial corneal dystrophy (FECD) is a genetically heterogeneous disease. Hypothesizing that cellular senescence may be relevant in FECD pathogenesis, genetically undifferentiated late-onset FECD endothelial samples were analyzed to identify common changes of specific senescence-related transcripts. Total RNA was extracted from 21 FECD endothelial samples retrieved from patients undergoing lamellar keratoplasty due to clinically diagnosed end-stage FECD and from 12 endothelial samples retrieved from normal autopsy eyes. Taqman low density array (TLDA) cards were used to analyze differential expression of 89 cellular senescence-related transcripts. Result validation was performed using individual real-time PCR assays. TLDA-analysis demonstrated differential expression of 31 transcripts (fold-change >1.5; p<0.05). Thereof, 27 showed significant up-regulation and 4 significant down-regulation. Markedly elevated mRNA-levels of the constitutively active and reactive oxygen species-generating enzyme NOX4 were found in all evaluable FECD samples. In addition, increased expression of CDKN2A and its transcriptional activators ETS1 and ARHGAP18 (SENEX) along with decreased expression of CDKN2A inhibitor ID1 were detected in FECD samples. Consistent over-expression of NOX4 in FECD endothelial samples suggests a role as pathogenic factor and as a potential new treatment target in FECD. Transcriptional up-regulation of the CDKN2A-pathway provides further evidence for increased cellular senescence in FECD endothelium.

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Endothelial Cell MicroRNA Expression in Human Late-Onset Fuchs' Dystrophy

Cited by 58 publications

References 50 publications

Human Corneal MicroRNA Expression Profile in Fungal Keratitis

Human Corneal MicroRNA Expression Profile in Fungal Keratitis

Fuchs Corneal Dystrophy

Transcript profile of cellular senescence-related genes in Fuchs endothelial corneal dystrophy

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