{"doi":"10.1016/j.jbc.2025.110538","title":"Inactivation of cellular retinol-binding protein 1 protects against bis-retinoid accumulation and light-induced retinal degeneration in mice","abstract":"Delayed clearance of all- trans -retinal (at-RAL) in photoreceptors is linked to prevalent retinal diseases such as Stargardt disease, rod-cone dystrophies, and age-related macular degeneration. Pharmacological modulation of retinoid metabolism in the eye presents a promising therapeutic strategy, with cellular retinol-binding protein 1 (RBP1) emerging as a potential target. However, it lacks genetic validation as a therapeutic target in an animal model of human disease. Thus, we investigated the effect of the Rbp1 gene inactivation on the phenotype of the Abca4 -/- /Rdh8 -/- model of Stargardt disease. Triple knockout ( Abca4 -/- /Rdh8 -/- /Rbp1 -/- ) mice were protected against light-induced retinal degeneration. RBP1 deficiency also slowed bis-retinoid accumulation in aged animals. Furthermore, pharmacological inhibition of RBP1 alleviated the retinal degeneration phenotype. These findings provide both genetic and pharmacological evidence supporting RBP1 as a promising therapeutic target for retinal degenerative diseases associated with impaired at-RAL clearance.","journal":"Journal of Biological Chemistry","year":2025,"id":571214,"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":0.9561,"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":1409900,"name":"Jaclyn Swigris","orcid":null,"position":1,"is_corresponding":false},{"id":760451,"name":"Jacqueline Plau","orcid":null,"position":2,"is_corresponding":false},{"id":1408675,"name":"Chloe Chung","orcid":null,"position":3,"is_corresponding":false},{"id":1477052,"name":"Anna Walczak","orcid":"0000-0002-4060-3514","position":4,"is_corresponding":false},{"id":324003,"name":"Beata Jastrzębska","orcid":"0000-0001-5209-8685","position":5,"is_corresponding":false},{"id":485236,"name":"William S. Blaner","orcid":"0000-0002-9847-7506","position":6,"is_corresponding":false},{"id":337166,"name":"Marcin Golczak","orcid":"0000-0001-7477-4357","position":7,"is_corresponding":false},{"id":759918,"name":"Made Airanthi K. Widjaja‐Adhi","orcid":"0000-0002-0589-2605","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T02:57:15.755535Z","pmid":"40749832","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":[]}