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Adult onset cataract formation following loss of miR-26 results from deregulated inflammation and loss of epithelial homeostasis

ABSTRACT: Despite strong evidence that normal lens development and function requires regulation governed by miRNAs, the role of specific miRNAs in mammalian lens FEV development and homeostasis remains largely unexplored. Here we undertook a comprehensive RNA-seq analysis of miRNA transcripts in the newborn mouse lens, exploring both differential expression between lens epithelial cells and lens fiber cells and overall miRNA abundance. We then selected the three most abundant lens miRNAs: miR-184, miR-1 and miR-26 for functional analysis. Of these three miRNAs, only miR-1, which was highly expressed in lens fiber cells, exhibited significant differential expression. Mouse lenses lacking miR-184, or both copies of miR-1, or all three copies of miR-26 exhibited morphologically normal prenatal lens development. However, mice lacking all three copies of miR-26 (miR-26KO) developed postnatal cataracts at approximately 4-6 weeks of age. RNA-seq analysis of neonatal lenses from miR-26KO mice demonstrated a deregulation of the complement pathway, inflammation and epithelial to mesenchymal transition

ORGANISM(S): Mus musculus

PROVIDER: GSE252611 | GEO | 2024/05/08

REPOSITORIES: GEO

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Adult onset cataract formation following loss of miR-26 results from deregulated inflammation and loss of epithelial homeostasis

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