Comparative transcriptome and network biology analyses demonstrate antiproliferative and hyperapoptotic phenotypes in human keratoconus corneas
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Updated: May 31, 2026
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Published on: February 15, 2019
Matthias Macé1, Stéphane D Galiacy, Angélique Erraud
1INSERM (Institut National de Santé et de Recherche Médicale), U563, Toulouse, France. matthias.mace@inserm.fr
Purpose:
To decipher the biological pathways involved in keratoconus pathophysiology by determining the patterns of differential gene expression between keratoconus and control corneas.
Methods:
RNA was extracted from surgically removed corneas of 10 keratoconus patients and from normal corneas of 10 control patients who had undergone enucleation of an eye for ocular melanoma. Several hundred thousand RNA transcripts were assessed using exon microarrays. Statistical comparison and identification of differentially regulated and differentially spliced RNA transcripts was performed by comparing keratoconus cases and controls. In addition, relevant biological pathways were identified by information extraction using network biology.
Results:
Eighty-seven genes showed significant differences in expression levels. Among these, 69 were downregulated in keratoconus patients, particularly partners of the transcription factor AP-1. The 18 overexpressed genes include mucins, keratins, and genes involved in fibroblast proliferation. In addition, 36 genes were shown to be differentially spliced, including 9 among those that were differentially expressed. Network biology and analysis using Gene Ontology descriptors suggest that many members of both groups belong to pathways of apoptosis and regulation of the balance between cellular differentiation and proliferation.
Conclusions:
This work constitutes the first genome-wide transcriptome analysis of keratoconus patient corneas that include all currently known genes and exons. Differential expression suggests that mechanisms of cell loss resulting from antiproliferative and hyperapoptotic phenotypes may be responsible for the pathogenesis of keratoconus. Array information, experimental design, raw intensities, and processed log(2) ratios were deposited at the European Bioinformatic Institute's ArrayExpress database (http://www.ebi.ac.uk/arrayexpress/). The accession number is E-MEXP-2777.
Insights
This study reveals significant gene expression differences in keratoconus corneas, suggesting cell loss via antiproliferative and hyperapoptotic pathways contribute to keratoconus (KC) disease. This research provides new insights into KC pathophysiology.
Area of Science:
- Ophthalmology and Genetics
- Molecular Biology
- Transcriptomics
Background:
- Keratoconus (KC) is a progressive corneal ectasia of unknown etiology.
- Understanding the molecular mechanisms underlying KC is crucial for developing targeted therapies.
- Genome-wide gene expression analysis can identify key pathways involved in disease pathogenesis.
Purpose of the Study:
- To identify differentially expressed genes and biological pathways in keratoconus corneas compared to normal controls.
- To elucidate the molecular underpinnings of keratoconus pathophysiology through transcriptome analysis.
Main Methods:
- RNA extraction from surgically removed keratoconus (n=10) and control (n=10) corneas.
- Exon microarray analysis to assess hundreds of thousands of RNA transcripts.
- Statistical comparison for differential gene expression and splicing; network biology for pathway identification.
Main Results:
- Eighty-seven genes exhibited significant expression level differences.
- 69 genes were downregulated in keratoconus, including AP-1 transcription factor partners.
- 18 genes were overexpressed (e.g., mucins, keratins); 36 genes showed differential splicing, impacting apoptosis and cell proliferation/differentiation balance.
Conclusions:
- This is the first genome-wide transcriptome analysis of keratoconus corneas.
- Differential gene expression suggests antiproliferative and hyperapoptotic mechanisms contribute to keratoconus pathogenesis.
- Findings provide a foundation for further research into keratoconus molecular mechanisms and potential therapeutic targets.
