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bioRxiv · 10.1101/2024.01.29.577818

miR-26 deficiency causes alterations in lens transcriptome and results in adult-onset cataract

Upreti, A.·Hoang, T. V.·Li, M.·Tangeman, J. A.·Dierker, D. S.·Wagner, B. D.·Tsonis, P. A.·Liang, C.·Lachke, S. A.·Robinson, M. L.
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Abstract

PurposeDespite strong evidence demonstrating that normal lens development requires regulation governed by miRNAs, the functional role of specific miRNAs in mammalian lens development remains largely unexplored. MethodsA comprehensive 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 was conducted by miRNA-seq. Mouse lenses lacking each of three abundantly expressed lens miRNAs: miR-184, miR-26 and miR-1 were analyzed to explore the role of these miRNAs in lens development. ResultsMice lacking all three copies of miR-26 (miR-26TKO) developed postnatal cataracts as early as 4-6 weeks of age. RNA-seq analysis of neonatal lenses from miR-26TKO mice exhibited abnormal reduced expression of a cohort of genes found to be lens-enriched and linked to cataract (e.g. Foxe3, Hsf4, Mip, Tdrd7, and numerous crystallin genes), and abnormal elevated expression of genes related to neural development (Lhx3, Neurod4, Shisa7, Elavl3), inflammation (Ccr1, Tnfrsf12a, Csf2ra), the complement pathway, and epithelial to mesenchymal transition (Tnfrsf1a, Ccl7, Stat3, Cntfr). ConclusionmiR-1, miR-184 and miR-26 are each dispensable for normal embryonic lens development. However, loss of miR-26 causes lens transcriptome changes and drives cataract formation.

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Upreti, A., Hoang, T. V., Li, M., Tangeman, J. A., Dierker, D. S., Wagner, B. D., Tsonis, P. A., Liang, C., Lachke, S. A., Robinson, M. L.. 2024-01-30. miR-26 deficiency causes alterations in lens transcriptome and results in adult-onset cataract. https://doi.org/10.1101/2024.01.29.577818

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