{"doi":"10.3390/brainsci15020123","title":"Ouabain Counteracts Retinal Ganglion Cell Death Through Modulation of BDNF and IL-1 Signaling Pathways","abstract":"Background: Ouabain is a steroid hormone that binds to the sodium pump (Na+, K+-ATPase) at physiological (nanomolar) concentrations, activating different signaling pathways. This interaction has been shown to prevent the axotomy-induced death of retinal ganglion cells (RGCs), although the underlying mechanisms remain unclear. Objective: In this study, we investigated potential mechanisms by which ouabain promotes RGC survival using primary cultures of rat neural retina. Results: Our findings indicate that ouabain regulates brain-derived neurotrophic factor (BDNF) signaling in retinal cells via matrix metalloproteinase-9-mediated processing of proBDNF to mature BDNF (mBDNF) and by increasing the phosphorylation of the mBDNF receptor, tropomyosin-related receptor kinase B. Ouabain also enhances the maturation of interleukin (IL)-1β through the increased activation of caspase-1, which mediates the processing of proIL-1β into IL-1β, and transiently upregulates both IL-1 receptor and IL-1 receptor antagonist (IL-1Ra). Treatment using either IL-1β or IL-1Ra alone is sufficient to enhance RGC survival similarly to that achieved with ouabain. Finally, we further show that ouabain prevents RGC death through a complex signaling mechanism shared by BDNF and IL-1β, which includes the activation of the Src and protein kinase C pathways. Conclusions: Collectively, these results suggest that ouabain stimulates the maturation and signaling of both BDNF and IL-1β, which act as key mediators of RGC survival.","journal":"Brain Sciences","year":2025,"id":551336,"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":0.9555,"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":1447135,"name":"Camila Saggioro de Figueiredo","orcid":"0000-0001-5262-231X","position":1,"is_corresponding":false},{"id":1447482,"name":"Ícaro Raony","orcid":null,"position":2,"is_corresponding":false},{"id":1447483,"name":"Juliana Salles von-Held-Ventura","orcid":null,"position":3,"is_corresponding":false},{"id":1447136,"name":"Marcelo Gomes Granja","orcid":"0000-0001-6243-0768","position":4,"is_corresponding":false},{"id":1447484,"name":"Thalita Mázala-de-Oliveira","orcid":null,"position":5,"is_corresponding":false},{"id":1447485,"name":"Vinícius Henrique Pedrosa-Soares","orcid":null,"position":6,"is_corresponding":false},{"id":1447137,"name":"Aline Araújo dos Santos","orcid":"0000-0002-4199-9821","position":7,"is_corresponding":false},{"id":1447138,"name":"Elizabeth Giestal‐de‐Araujo","orcid":"0000-0001-6583-6237","position":8,"is_corresponding":false},{"id":1447481,"name":"Amanda Cândida da Rocha Oliveira","orcid":null,"position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:54:25.065895Z","pmid":"40002456","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":[]}