{"doi":"10.1101/2024.01.29.577818","title":"miR-26 deficiency causes alterations in lens transcriptome and results in adult-onset cataract","abstract":"Abstract Purpose Despite 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. Methods A 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. Results Mice lacking all three copies of miR-26 ( miR-26 TKO ) developed postnatal cataracts as early as 4-6 weeks of age. RNA-seq analysis of neonatal lenses from miR-26 TKO 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 ). Conclusion miR-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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":493800,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8841,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":413525,"name":"Thanh Hoang","orcid":"0000-0002-7666-3842","position":1,"is_corresponding":false},{"id":1296473,"name":"Minghua Li","orcid":"0000-0001-7373-6535","position":2,"is_corresponding":false},{"id":1176357,"name":"Jared A. Tangeman","orcid":"0000-0002-0224-2893","position":3,"is_corresponding":false},{"id":1296829,"name":"David S. Dierker","orcid":null,"position":4,"is_corresponding":false},{"id":1296474,"name":"Brad D. Wagner","orcid":"0000-0001-8486-8496","position":5,"is_corresponding":false},{"id":736667,"name":"Panagiotis A. Tsonis","orcid":null,"position":6,"is_corresponding":false},{"id":258207,"name":"Chun Liang","orcid":"0000-0003-1996-6027","position":7,"is_corresponding":false},{"id":499776,"name":"Salil A. Lachke","orcid":"0000-0001-8845-010X","position":8,"is_corresponding":false},{"id":1130230,"name":"Michael L. Robinson","orcid":"0000-0003-4779-3426","position":9,"is_corresponding":false},{"id":1296472,"name":"Anil Upreti","orcid":"0000-0001-8502-6506","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:09:03.883685Z","pmid":"38352453","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}