MiRNA profile in normal and aniridia conjunctival cells versus severity of aniridia‐associated keratopathy

Abstract

AbstractPatients with congenital aniridia develop aniridia‐associated keratopathy (AAK), most of them exhibiting a similar disease mechanism namely haploinsufficiency of the PAX6 gene. The clinical onset and progression of AAK is quite diverse across patients. MiRNAs may act as regulatory elements affecting AAK progression. In mouse animal models the role of miRNAs controlling corneal vascularization has come into research focus. Interestingly, some of the miRNAs involved in neovascularization of the cornea, such as miR‐204, are regulated by PAX6 expression. The aim of this study was to identify deregulated miRNAs in conjunctival cells of AKK patients compared to unaffected controls, also in context with PAX6 haploinsufficiency. We further attempted to correlate miRNA expression with clinical severity of AKK (Staging ranging from 0 intact limbus, no pannus, clear cornea to 4 – end‐stage, thick, white, opaque vascularized pannus). We analyzed the miRNA expression profile in conjunctival cells of 20 patients with AKK and 20 age and sex matched controls using microarrays. We identified 10 down‐ and 11 upregulated miRNAs, including downregulated miR‐204‐5p and upregulated mir‐375. The latter miRNA has been reported to bind in PAX6 3′ UTR. Two patients showed mir‐204‐5p expression levels similar to healthy controls. These patients had mutations in PAX6 flanking genes likely affecting PAX6 regulatory regions and 0‐1 severity of AAK phenotype. Our results show strong expression changes in miRNA profile of Aniridia patients.