{"doi":"10.1167/iovs.65.14.33","title":"Proteomic Alterations in Retinal Müller Glial Cells Lacking Interleukin-6 Receptor: A Comprehensive Analysis","abstract":"Purpose: Interleukin-6 (IL-6) is an inflammatory cytokine implicated in various retinal pathologies and functions primarily through two signaling pathways: cis-signaling via IL-6 binding to its membrane-bound receptor (IL-6Rα), and trans-signaling via IL-6 binding to soluble IL-6 receptor (sIL-6R). Because the differential effects of IL-6 signaling in retinal Müller glial cells (MGCs) remain unclear, we generated an MGC-specific Il6ra-/- knockout (KO) mouse to eliminate IL-6Rα and, consequently, IL-6 cis-signaling in MGCs. In this study, we examined the proteomic changes in MGCs isolated from KO mice lacking a functional IL-6Rα. Methods: The proteomes of MGCs isolated from wild-type (WT) and KO mice were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and validated by parallel reaction monitoring (PRM). Relevant biological functions and pathways were examined using Gene Ontology and Ingenuity Pathway Analysis. Results: LC-MS/MS detected 1866 proteins, of which 81 were significantly altered (41 upregulated, 40 downregulated). PRM analysis confirmed differential expression of Ptgis (fold change [FC] = 3.63), Dpep1 (FC = 2.79), Fmo1 (FC = 2.77), Igfbp7 (FC = 2.07), Rpb1 (FC = 1.73), Pygp (FC = 1.46), Niban 1 (FC = 0.58), Mest (FC = 0.48), and Aldh3a1 (FC = 0.30). The significantly altered proteins are involved in oxidative stress balance, inflammation, mitochondrial dysfunction, and regulation of vascular endothelial growth factor (VEGF) signaling. Conclusions: The absence of IL-6Rα in KO MGCs corresponded to significant changes in their proteomic profile, highlighting the impact of autocrine IL-6 signaling on MGC function. This study provides a basis for future research evaluating distinct roles of IL-6 in MGCs and subsequent effects on retinal pathology.","journal":"Investigative Ophthalmology & Visual Science","year":2024,"id":472774,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":286445,"name":"Rebekah Robinson","orcid":"0000-0001-9234-6209","position":1,"is_corresponding":false},{"id":1224715,"name":"Neel Edupuganti","orcid":null,"position":2,"is_corresponding":false},{"id":1037378,"name":"Jeremy Altman","orcid":null,"position":3,"is_corresponding":false},{"id":1045890,"name":"Grace Greenway","orcid":null,"position":4,"is_corresponding":false},{"id":264780,"name":"Tae Jin Lee","orcid":"0000-0002-5245-1140","position":5,"is_corresponding":false},{"id":367348,"name":"Wenbo Zhi","orcid":"0000-0002-7720-7048","position":6,"is_corresponding":false},{"id":264781,"name":"Ashok Sharma","orcid":"0000-0001-9597-4374","position":7,"is_corresponding":false},{"id":286447,"name":"Shruti Sharma","orcid":"0000-0001-8200-108X","position":8,"is_corresponding":false},{"id":424363,"name":"J. David Glass","orcid":"0009-0003-1575-2192","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T02:05:57.032095Z","pmid":"39699914","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":[]}