{"doi":"10.1172/jci.insight.145715","title":"αVβ8 integrin targeting to prevent posterior capsular opacification","abstract":"Fibrotic posterior capsular opacification (PCO), a major complication of cataract surgery, is driven by transforming growth factor-β (TGF-β). Previously, αV integrins were found to be critical for the onset of TGF-β-mediated PCO in vivo; however, the functional heterodimer was unknown. Here, β8 integrin-conditional knockout (β8ITG-cKO) lens epithelial cells (LCs) attenuated their fibrotic responses, while both β5 and β6 integrin-null LCs underwent fibrotic changes similar to WT at 5 days post cataract surgery (PCS). RNA-Seq revealed that β8ITG-cKO LCs attenuated their upregulation of integrins and their ligands, as well as known targets of TGF-β-induced signaling, at 24 hours PCS. Treatment of β8ITG-cKO eyes with active TGF-β1 at the time of surgery rescued the fibrotic response. Treatment of WT mice with an anti-αVβ8 integrin function blocking antibody at the time of surgery ameliorated both canonical TGF-β signaling and LC fibrotic response PCS, and treatment at 5 days PCS, after surgically induced fibrotic responses were established, largely reversed this fibrotic response. These data suggest that αVβ8 integrin is a major regulator of TGF-β activation by LCs PCS and that therapeutics targeting αVβ8 integrin could be effective for fibrotic PCO prevention and treatment.","journal":"JCI Insight","year":2021,"id":176747,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.963,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":617605,"name":"Samuel G. Novo","orcid":"0000-0002-6400-0013","position":1,"is_corresponding":false},{"id":356348,"name":"Yan Wang","orcid":"0000-0002-1257-6635","position":2,"is_corresponding":false},{"id":12168,"name":"Dean Sheppard","orcid":"0000-0002-6277-2036","position":3,"is_corresponding":false},{"id":650062,"name":"Amha Atakilit","orcid":"0000-0002-8586-7230","position":4,"is_corresponding":false},{"id":251034,"name":"Thomas D. Arnold","orcid":"0000-0002-7310-5597","position":5,"is_corresponding":false},{"id":720125,"name":"Nicole M. Rossi","orcid":null,"position":6,"is_corresponding":false},{"id":356349,"name":"Adam Faranda","orcid":"0000-0001-6993-8361","position":7,"is_corresponding":false},{"id":356350,"name":"Melinda K. Duncan","orcid":"0000-0003-1570-322X","position":8,"is_corresponding":false},{"id":719556,"name":"Mahbubul H. Shihan","orcid":"0000-0001-5190-389X","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-18T23:47:23.605867Z","pmid":"34554928","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":[]}