{"doi":"10.1167/iovs.64.15.1","title":"Diabetic Müller-Glial-Cell-Specific <i>Il6ra</i> Knockout Mice Exhibit Accelerated Retinal Functional Decline and Thinning of the Inner Nuclear Layer","abstract":"Purpose: Interleukin-6 (IL-6) is implicated in the pathology of diabetic retinopathy (DR). IL-6 trans-signaling via soluble IL-6 receptor (IL-6R) is primarily responsible for its pro-inflammatory functions, whereas cis-signaling via membrane-bound IL-6R is anti-inflammatory. Using a Müller-glial-cell-specific Il6ra-/- mouse, we examined how loss of IL-6 cis-signaling in Müller glial cells (MGCs) affected retinal thinning and electroretinography (ERG) response over 9 months of diabetes. Methods: Diabetes was induced in wildtype and knockout mice with streptozotocin (40 mg/kg, daily for 5 days). Spectral domain optical coherence tomography (SD-OCT), ERG, and fundoscopy/fluorescein angiography (FA) were assessed at 2, 6, and 9 months of diabetes. MGCs and bipolar neurons were examined in retinal tissue sections by immunofluorescence. Results: Diabetic MGC Il6ra-/- mice had significantly thinner retinas than diabetic wildtype mice at 2 (-7.6 µm), 6 (-12.0 µm), and 9 months (-5.0 µm) of diabetes, as well as significant thinning of the inner nuclear layer (INL). Diabetic MGC Il6ra-/- mice also showed a reduction in scotopic B-wave amplitude and B-wave/A-wave ratio earlier than wildtype diabetic mice. In retinal sections, we found a decrease in bipolar neuronal marker PKCα only in diabetic MGC Il6ra-/- mice, which was significantly lower than both controls and diabetic wildtype mice. Glutamine synthetase, a Müller cell marker, was reduced in both wildtype and MGC Il6ra-/- diabetic mice compared to their respective controls. Conclusions: IL-6 cis-signaling in MGCs contributes to maintenance of the INL in diabetes, and loss of the IL-6 receptor reduces MGC-mediated neuroprotection of bipolar neurons in the diabetic retina.","journal":"Investigative Ophthalmology & Visual Science","year":2023,"id":341942,"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":0.9583,"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":286445,"name":"Rebekah Robinson","orcid":"0000-0001-9234-6209","position":1,"is_corresponding":false},{"id":1045890,"name":"Grace Greenway","orcid":null,"position":2,"is_corresponding":false},{"id":778803,"name":"Garrett Jones","orcid":null,"position":3,"is_corresponding":false},{"id":286447,"name":"Shruti Sharma","orcid":"0000-0001-8200-108X","position":4,"is_corresponding":false},{"id":424363,"name":"J. David Glass","orcid":"0009-0003-1575-2192","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T01:11:08.077724Z","pmid":"38038619","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":[]}