Comparative transcriptome and network biology analyses demonstrate antiproliferative and hyperapoptotic phenotypes in human keratoconus corneas.

摘要: PURPOSE: To decipher the biological pathways involved in keratoconus pathophysiology by determining patterns of differential gene expression between and control corneas. METHODS: RNA was extracted from surgically removed corneas 10 patients normal who had undergone enucleation an eye for ocular melanoma. Several hundred thousand transcripts were assessed using exon microarrays. Statistical comparison identification differentially regulated spliced performed comparing cases controls. In addition, relevant identified information extraction network biology. RESULTS: Eighty-seven genes showed significant differences levels. Among these, 69 downregulated patients, particularly partners transcription factor AP-1. The 18 overexpressed include mucins, keratins, fibroblast proliferation. 36 shown to be spliced, including 9 among those that expressed. Network biology analysis Gene Ontology descriptors suggest many members both groups belong apoptosis regulation balance cellular differentiation CONCLUSIONS: This work constitutes first genome-wide transcriptome patient all currently known exons. Differential suggests mechanisms cell loss resulting antiproliferative hyperapoptotic phenotypes may responsible pathogenesis keratoconus. Array information, experimental design, raw intensities, processed log(2) ratios deposited at European Bioinformatic Institute's ArrayExpress database (http://www.ebi.ac.uk/arrayexpress/). accession number is E-MEXP-2777.