{"doi":"10.1016/j.ajpath.2025.10.006","title":"Silencing Ubiquitin-Specific Peptidase 10 Alleviates Persistent Corneal Epithelial Defect in Mice","abstract":"Persistent corneal epithelial defect (PCED) is a condition in which the corneal epithelium fails to heal properly after injury resulting in vision loss. Previous studies demonstrate that the deubiquitinase, USP10 is a key regulator of wound healing and scarring in the cornea. Here we utilized a highly modified in vivo self-delivering siRNA (sdRNA) targeting USP10 in a mouse model of PCED. In this model the corneal epithelium is scraped from the basement membrane and although the wound initially closes, the epithelium re-opens at day 28, thereby modeling a persistent corneal defect. Our studies revealed that one dose of USP10-targeting sdRNA after wounding prevented reopening of the wound at day 28. Optical Coherence Tomography (OCT) images, H&E staining, and immunohistochemistry demonstrated improved corneal morphology, normal epithelial stratification of the regrown epithelium, with re-establishment of hemidesmosomes and reduced scarring and inflammation (CD45+ cells). Correspondingly, RNA-Seq of the regenerated corneal epithelium revealed that USP10 knockdown altered gene expression and pathways controlling tissue repair. Specifically, cell proliferation pathways were enhanced, while extracellular matrix, integrin, and immune cell signatures that lead to scar formation were reduced. Our results demonstrate that a one-time application of in vivo sdRNA targeting USP10 is a novel method to prevent epithelial wound re-opening and subsequent scarring and inflammation and may be useful to promote regenerative healing in other tissues.","journal":"American Journal Of Pathology","year":2025,"id":580297,"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":0.9573,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1491110,"name":"Mohammad Anjum Shaik","orcid":"0009-0002-0819-5319","position":1,"is_corresponding":false},{"id":1140778,"name":"Christine Tilstra-Smith","orcid":"0009-0005-3869-8154","position":2,"is_corresponding":false},{"id":414825,"name":"Nileyma Castro","orcid":null,"position":3,"is_corresponding":false},{"id":851152,"name":"Jelissa Reynoso-García","orcid":"0000-0002-5285-6295","position":4,"is_corresponding":false},{"id":1003471,"name":"Michael E. Zuber","orcid":"0000-0001-8257-9033","position":5,"is_corresponding":false},{"id":413517,"name":"Audrey M. Bernstein","orcid":"0000-0002-2537-2594","position":6,"is_corresponding":false},{"id":939304,"name":"Audreesh Banerjee","orcid":"0009-0002-1283-4822","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T02:58:38.868285Z","pmid":"41205807","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":[]}