{"doi":"10.1038/s42003-025-08534-6","title":"OPTN protects retinal ganglion cells and ameliorates neuroinflammation in optic neuropathies","abstract":"Optineurin (OPTN) is an adaptor protein that plays a crucial role in many cellular pathways, including NF-κB signaling, programmed cell death, and vesicular trafficking. OPTN dysfunction has been implicated in the pathogenesis of several diseases, such as primary open angle glaucoma (POAG), amyotrophic lateral sclerosis (ALS). While mutations of OPTN seem to be predominantly loss-of-function in ALS, only gain-of-function mechanisms have been reported in POAG. Here, we demonstrate that OPTN knockout in the retina contributes to short-term astrogliosis, retinal ganglion cell (RGC) loss and long-term microglial activation. Moreover, OPTN loss of function does not exacerbate RGC death induced by ocular hypertension. Integrated bioinformatics and immunofluorescence analyses reveal that OPTN dysfunction leads to neuropeptide Y (NPY) downregulation and CHOP upregulation. Overexpression of wild-type OPTN in a hypertension glaucoma model prevents the RGC loss and attenuates microglial activation. Together, our findings highlight a neuroprotective role for OPTN as a key neuroimmune modulator. OPTN dysfunction induces short-term astrogliosis and long-term microglial activation, driving IOP-independent RGC loss that contributes to normal tension and hypertensive glaucoma; OPTN overexpression alleviates neuroinflammation and neurodegeneration.","journal":"Communications Biology","year":2025,"id":547716,"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":0.9551,"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":1440517,"name":"Yiqi Wang","orcid":"0009-0002-4989-3674","position":1,"is_corresponding":false},{"id":379362,"name":"Yong‐hui Jiang","orcid":"0000-0001-6188-8806","position":2,"is_corresponding":false},{"id":985769,"name":"Ryan Donahue","orcid":"0000-0003-2519-0763","position":3,"is_corresponding":false},{"id":1440938,"name":"Gaby Cao","orcid":null,"position":4,"is_corresponding":false},{"id":1440939,"name":"Weixuan Yan","orcid":null,"position":5,"is_corresponding":false},{"id":1440518,"name":"Hong Guo","orcid":"0009-0000-9826-4044","position":6,"is_corresponding":false},{"id":644058,"name":"Zhenghui Li","orcid":"0000-0002-9791-9333","position":7,"is_corresponding":false},{"id":1440940,"name":"Jenna Liang","orcid":null,"position":8,"is_corresponding":false},{"id":805593,"name":"Jin Hao","orcid":"0000-0002-6685-2017","position":9,"is_corresponding":false},{"id":1256462,"name":"Yi Lu","orcid":"0000-0001-6960-461X","position":10,"is_corresponding":false},{"id":463612,"name":"Fengfeng Bei","orcid":"0000-0002-6084-5342","position":11,"is_corresponding":false},{"id":985766,"name":"Qianbin Wang","orcid":"0000-0002-9840-6732","position":12,"is_corresponding":false},{"id":263828,"name":"Feng Tian","orcid":"0000-0001-8965-8973","position":13,"is_corresponding":false},{"id":913191,"name":"Qinglong Wang","orcid":"0000-0002-3074-4786","position":0,"is_corresponding":true}],"reference_count":104,"raw_metadata":null,"created_at":"2026-07-19T02:53:53.962932Z","pmid":"41102382","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":[]}