{"doi":"10.1101/2025.02.12.637499","title":"MicroRNA-34a suppresses KLF2 to promote pathological angiogenesis through the CXCR4/CXCL12 pathway in age-related macular degeneration","abstract":"Age-related macular degeneration (AMD), characterized by pathologic choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. Vascular endothelial growth factor A (VEGFa) antagonists can prevent acute vision loss, but high treatment burden and loss of efficacy with chronic therapy highlight the need to explore alternative mechanisms. Recently, microRNA-34a (miR-34a) has emerged as a key regulator in aging and age-related diseases, but its role in neovascular AMD is unclear. In an injury-induced murine CNV model, we discovered miR-34a promoted pathological angiogenesis, without altering expression of Vegfa or its receptor Kdr, the canonical regulators of CNV. Mechanistically, miR-34a directly targets and inhibits the transcription factor KLF2 thereby upregulating the pro-angiogenic factors CXCR4 and CXCL12. Finally, we show miR-34a exacerbates CNV in aged mice and is expressed in CNV lesions excised from wet AMD patients. These findings establish a causal link between the age-related miR-34a and neovascularization in AMD. Teaser: Identification of a molecular mechanism involved in the pathogenesis of a prevalent and debilitating age-related ocular disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":562152,"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":0.9537,"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":564524,"name":"Joseph B. Lin","orcid":"0000-0001-6667-9018","position":1,"is_corresponding":false},{"id":1030858,"name":"Ryo Terao","orcid":"0000-0001-6182-4343","position":2,"is_corresponding":false},{"id":564522,"name":"Tae Jun Lee","orcid":"0000-0003-2699-2573","position":3,"is_corresponding":false},{"id":328040,"name":"Andrea Santeford","orcid":"0000-0002-7691-6213","position":4,"is_corresponding":false},{"id":328045,"name":"Rajendra S. Apte","orcid":"0000-0003-2281-2336","position":5,"is_corresponding":false},{"id":1206935,"name":"Jason Colasanti","orcid":"0000-0002-7151-0011","position":0,"is_corresponding":true}],"reference_count":105,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:56:05.550545Z","pmid":"39990324","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":[]}