{"doi":"10.3390/ijms232214196","title":"3K3A-Activated Protein C Prevents Microglia Activation, Inhibits NLRP3 Inflammasome and Limits Ocular Inflammation","abstract":"3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with pleiotropic cytoprotective properties albeit without the bleeding risks. The anti-inflammatory activities of 3K3A-APC were demonstrated in multiple preclinical injury models, including various neurological disorders. We determined the ability of 3K3A-APC to inhibit ocular inflammation in a murine model of lipopolysaccharide (LPS)-induced uveitis. Leukocyte recruitment, microglia activation, NLRP3 inflammasome and IL-1β levels were assessed using flow cytometry, retinal cryosection histology, retinal flatmount immunohistochemistry and vascular imaging, with and without 3K3A-APC treatment. LPS triggered robust inflammatory cell recruitment in the posterior chamber. The 3K3A-APC treatment significantly decreased leukocyte numbers and inhibited leukocyte extravasation from blood vessels into the retinal parenchyma to a level similar to controls. Resident microglia, which underwent an inflammatory transition following LPS injection, remained quiescent in eyes treated with 3K3A-APC. An inflammation-associated increase in retinal thickness, observed in LPS-injected eyes, was diminished by 3K3A-APC treatment, suggesting its clinical relevancy. Finally, 3K3A-APC treatment inhibited inflammasome activation, determined by lower levels of NLRP3 and its downstream effector IL-1β. Our results highlight the anti-inflammatory properties of 3K3A-APC in ocular inflammation and suggest its potential use as a novel treatment for retinal diseases associated with inflammation.","journal":"International Journal of Molecular Sciences","year":2022,"id":269833,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":776900,"name":"Gil Ben-David","orcid":"0000-0001-9993-1005","position":1,"is_corresponding":false},{"id":776899,"name":"Yehonatan Weinberger","orcid":"0000-0002-5923-769X","position":2,"is_corresponding":false},{"id":933478,"name":"Rabeei Haj Daood","orcid":null,"position":3,"is_corresponding":false},{"id":483071,"name":"José A. Fernández","orcid":"0000-0002-0804-1865","position":4,"is_corresponding":false},{"id":776903,"name":"Ivan Budnik","orcid":"0000-0002-6652-2667","position":5,"is_corresponding":false},{"id":479524,"name":"Sarina Levy‐Mendelovich","orcid":"0000-0003-3971-0336","position":6,"is_corresponding":false},{"id":776902,"name":"Gili Kenet","orcid":"0000-0003-3494-9823","position":7,"is_corresponding":false},{"id":777565,"name":"Yael Nisgav","orcid":null,"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":776901,"name":"Dahlia Palevski","orcid":"0000-0001-9661-5680","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T00:27:22.602796Z","pmid":"36430674","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":[]}