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This study investigated the role of M\u00fcller glial spleen tyrosine kinase (SYK) in diabetes\u2010induced retinal complications. Hyperglycemic culture conditions increased mitochondrial membrane permeability and cytosolic mitochondrial DNA content in human MIO\u2010M1 M\u00fcller cells and enhanced cyclic GMP\u2013AMP synthase (cGAS)\u2013stimulator of interferon genes (STING) signaling, nuclear factor\u2010\u03baB (NF\u2010\u03baB) activation, and inflammatory cytokine expression. STING inhibition reduced inflammatory cytokine expression in cells exposed to hyperglycemic conditions by acting downstream of the increase in cytosolic mitochondrial DNA levels. In cells exposed to either hyperglycemic conditions or the STING agonist diABZI, SYK signaling was necessary for cGAS\u2010STING pathway activation. Inhibition of SYK\u2010dependent cGAS\u2010STING signaling reduced the expression of inflammatory cytokines, including IL1\u03b2, CCL2, and CCL5, under hyperglycemic conditions. In the retina of diabetic mice, M\u00fcller glia\u2010specific SYK deletion reduced glial activation and attenuated inflammatory cytokine expression. M\u00fcller glia\u2010specific SYK deletion also prevented diabetes\u2010induced retinal thinning and visual function deficits in spatial frequency threshold and contrast sensitivity. The data support an essential role for M\u00fcller glial SYK in diabetes\u2010induced retinal inflammation and the development of functional deficits in vision.<\/jats:p>","DOI":"10.1002\/glia.70155","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T12:00:55Z","timestamp":1776081655000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spleen Tyrosine Kinase (\n                    <scp>SYK<\/scp>\n                    ) is Necessary for\n                    <scp>cGAS<\/scp>\n                    \u2010\n                    <scp>STING<\/scp>\n                    Signaling in M\u00fcller Glia and Visual Function Deficits in Diabetic Mice"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0589-8353","authenticated-orcid":false,"given":"Esma I.","family":"Yerlikaya","sequence":"first","affiliation":[{"name":"Department of Cell and Biological Systems Penn State College of Medicine  Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3271-932X","authenticated-orcid":false,"given":"Siddharth","family":"Sunilkumar","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems Penn State College of Medicine  Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandeep M.","family":"Subrahmanian","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems Penn State College of Medicine  Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allyson L.","family":"Toro","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems Penn State College of Medicine  Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clay T.","family":"Yeager","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems Penn State College of Medicine  Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9071-2057","authenticated-orcid":false,"given":"Kashif A.","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems Penn State College of Medicine  Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward W.","family":"Harhaj","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems Penn State College of Medicine  Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alistair J.","family":"Barber","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems Penn State College of Medicine  Hershey Pennsylvania USA"},{"name":"Department of Ophthalmology Penn State College of Medicine  Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Dennis","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems Penn State College of Medicine  Hershey Pennsylvania USA"},{"name":"Department of Ophthalmology Penn State College of Medicine  Hershey Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.03.056"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-88698-3"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.1839"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.visres.2017.03.013"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.623058"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112207"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.07.001"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-020-00637-3"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20220990"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-1280"},{"key":"e_1_2_11_12_1","first-page":"1","article-title":"Contributions of Inflammatory Processes to the Development of the Early Stages of Diabetic Retinopathy","volume":"2007","author":"Kern T. 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