{"doi":"10.1016/j.ajpath.2025.11.009","title":"Mechanistic Insights into Glucocorticoid-Induced Ocular Hypertension Using Differences in Mouse Strain Responsiveness","abstract":"Glucocorticoids (GCs) are widely prescribed anti-inflammatory agents. Unfortunately, many people experience negative side-effects associated with long term GC therapy, developing GC-induced ocular hypertension (GC-OHT), which can lead to secondary glaucoma. Approximately, 40% of the treated individuals are susceptible to GC-OHT. Seventy years since this discovery, the molecular mechanisms underlying GC-OHT remain unclear. We previously developed a mouse model of GC-OHT delivering the potent GC dexamethasone (DEX) and observed strain-specific disparities in the development of GC-OHT. We now compare phenotypic and transcriptomic differences between five genetically distinct inbred mouse strains to identify biomarkers of GC susceptibility, and to better understand the molecular mechanisms of GC-OHT. Like humans, mouse strains differ in their ability to develop GC-OHT. Phenotypic characterization revealed that C57BL/6J and C3H/HeJ mice are GC responders and more susceptible to develop GC-OHT. DEX treatment in these strains led to elevated IOP compared to the GC non-responder strains DBA/2J. Gpnmb + , 129P3/J, and BALB/cJ. Transcriptomic analysis of responder and non-responder mouse strains revealed novel trabecular meshwork (TM) biomarkers of GC-OHT susceptibility involving enrichment of molecular pathways unique to this response. Our study identifies putative mechanisms underlying GC-OHT and provides insight into the pathogenesis of the clinically similar but more prevalent primary open-angle glaucoma.","journal":"American Journal Of Pathology","year":2025,"id":549463,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"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":390245,"name":"Gaurang Patel","orcid":"0000-0003-2497-665X","position":1,"is_corresponding":false},{"id":273527,"name":"J. Cameron Millar","orcid":"0000-0002-6963-500X","position":2,"is_corresponding":false},{"id":1444207,"name":"Sherri Feris","orcid":null,"position":3,"is_corresponding":false},{"id":1444208,"name":"Stacy Curry","orcid":null,"position":4,"is_corresponding":false},{"id":685152,"name":"Eldon E. Geisert","orcid":"0000-0003-0787-4416","position":5,"is_corresponding":false},{"id":273528,"name":"Abbot F. Clark","orcid":"0000-0003-3594-6560","position":6,"is_corresponding":false},{"id":273526,"name":"Pinkal D. Patel","orcid":"0000-0002-7704-4381","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T02:54:07.823422Z","pmid":"41407197","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":[]}