Abnormal neovascular and proliferative conjunctival phenotype in limbal stem cell deficiency is associated with altered microRNA and gene expression modulated by PAX6 mutational status in congenital aniridia

• DOI: 10.1016/j.jtos.2020.04.014
• Publication Date: 2020-05-16T02:33:47Z
• Authors: L. Latta; N. Ludwig; L. Krammes; T. Stachon; F.N. Fries; A. Mukwaya; N. Szentmáry; B. Seitz; B. Wowra; M. Kahraman; A. Keller; E. Meese; N. Lagali; B. Käsmann-Kellner
• Keywords: PAX6; Aniridia

To evaluate conjunctival cell microRNA (miRNAs) and mRNA expression in relation to observed phenotype of progressive limbal stem deficiency a cohort subjects with congenital aniridia known genetic status. Using impression cytology, bulbar cells were sampled from 20 age sex-matched healthy control subjects. RNA was extracted miRNA analyses performed using microarrays. Results related severity keratopathy cause aniridia. Of 2549 miRNAs, 21 differentially expressed relative controls (fold change ≤ -1.5 or ≥ +1.5). Among these miR-204–5p, an inhibitor corneal neovascularization, downregulated 26.8-fold severely vascularized corneas. At the level, 539 transcripts -2 +2), among FOSB FOS upregulated 17.5 9.7-fold respectively, JUN by 2.9-fold, all being components AP-1 transcription factor complex. Pathway analysis revealed enrichment PI3K-Akt, MAPK, Ras signaling pathways For several miRNAs regulating retinoic acid metabolism, levels correlated Strong dysregulation key factors at level suggests that conjunctiva is abnormally maintained pro-angiogenic proliferative state, changes are PAX6 mutation-dependent manner. Additionally, metabolism disrupted severe, but not mild forms