{"doi":"10.3390/ijms241310642","title":"3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1β, and Inflammatory Cell Accumulation in the Retina","abstract":"3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with cytoprotective properties and reduced bleeding risks. We studied the potential use of 3K3A-APC as a multi-target therapeutic option for choroidal neovascularization (CNV), a common cause of vision loss in age-related macular degeneration. CNV was induced by laser photocoagulation in a murine model, and 3K3A-APC was intravitreally injected. The impact of 3K3A-APC treatment on myeloid and microglia cell activation and recruitment and on NLRP3 inflammasome, IL-1β, and VEGF levels was assessed using cryosection, retinal flat-mount immunohistochemistry and vascular imaging. Additionally, we evaluated the use of fluorescein angiography as a surrogate marker for in vivo evaluation of the efficacy of 3K3A-APC treatment against leaking CNV lesions. Our results demonstrated that 3K3A-APC treatment significantly reduced the accumulation and activation of myeloid cells and microglia in the CNV area and decreased the NLRP3 and IL-1β levels at the CNV site and the surrounding retina. Furthermore, 3K3A-APC treatment resulted in leakage regression and CNV growth suppression. These findings indicate that the anti-inflammatory activities of 3K3A-APC contribute to CNV inhibition. Our study suggests the potential use of 3K3A-APC as a novel multi-target treatment for CNV.","journal":"International Journal of Molecular Sciences","year":2023,"id":365726,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":776903,"name":"Ivan Budnik","orcid":"0000-0002-6652-2667","position":1,"is_corresponding":false},{"id":777565,"name":"Yael Nisgav","orcid":null,"position":2,"is_corresponding":false},{"id":776901,"name":"Dahlia Palevski","orcid":"0000-0001-9661-5680","position":3,"is_corresponding":false},{"id":776900,"name":"Gil Ben-David","orcid":"0000-0001-9993-1005","position":4,"is_corresponding":false},{"id":483071,"name":"José A. Fernández","orcid":"0000-0002-0804-1865","position":5,"is_corresponding":false},{"id":1121996,"name":"Shany Nivinsky Margalit","orcid":null,"position":6,"is_corresponding":false},{"id":479524,"name":"Sarina Levy‐Mendelovich","orcid":"0000-0003-3971-0336","position":7,"is_corresponding":false},{"id":776902,"name":"Gili Kenet","orcid":"0000-0003-3494-9823","position":8,"is_corresponding":false},{"id":777566,"name":"Dov Weinberger","orcid":null,"position":9,"is_corresponding":false},{"id":379313,"name":"John H. Griffin","orcid":"0000-0002-4302-2547","position":10,"is_corresponding":false},{"id":776898,"name":"Tami Livnat","orcid":"0000-0002-1279-2557","position":11,"is_corresponding":false},{"id":776899,"name":"Yehonatan Weinberger","orcid":"0000-0002-5923-769X","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T01:14:50.885797Z","pmid":"37445820","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":[]}