Differential expression of salivary microRNA associated with keratoconus

Research into biomarkers has transformed the identification and management of many diseases. Keratoconus (KC) is a multifactorial corneal ectasia, and due to limited understanding of disease pathophysiology, no biomarkers have been fully validated. microRNAs (miRNAs) are involved in regulating gene expression. Differentially expressed miRNAs have been reported in KC corneal tissue and as biomarkers for other ocular disorders. Salivary biomarkers mirror systemic processes and saliva contains substantial miRNAs. However, it is unknown if salivary miRNAs are differentially expressed in KC. Salivary miRNAs were collected from healthy (n = 16) and KC subjects (n = 50) and measured by qRT-PCR. Upregulated gene expression of miR-939-5p, miR-26a-5p, miR-25-3p, and miR-92a-3p; and downregulated expression of miR-320a was observed. Bioinformatic analysis using Ingenuity Pathway Analysis identified 248 experimental validated miRNA target genes and an enriched subset of 16 genes uniquely related to KC corneal functions. Gene ontology analysis demonstrated the over-representation of genes involved in protein kinase complex, protein phosphorylation, cellular senescence, apoptosis, and stress response. Our data detected previously unknown KC-dependent dysregulation of salivary miRNA expression. Future studies are warranted to determine the viability of these miRNAs as possible KC biomarkers, and to further establish their pathophysiological function.