{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T19:27:41Z","timestamp":1787254061138,"version":"build-2736575974"},"reference-count":41,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201220"],"award-info":[{"award-number":["82201220"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Double Hundred Medical Youth Professionals Program of Wuxi Health Committee","award":["BJ2023002"],"award-info":[{"award-number":["BJ2023002"]}]},{"DOI":"10.13039\/501100005145","name":"Basic Research Program of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20241760"],"award-info":[{"award-number":["BK20241760"]}],"id":[{"id":"10.13039\/501100005145","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wuxi Taihu Lake Talent Plan","award":["2020-THRC-DJ-1"],"award-info":[{"award-number":["2020-THRC-DJ-1"]}]},{"name":"Wuxi Taihu Lake Talent Plan","award":["2020-THRCTD-1"],"award-info":[{"award-number":["2020-THRCTD-1"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Diabetic retinopathy (DR) is a major cause of vision loss in working-age adults with diabetes. Increasing evidence implicates neuroinflammation as a vital element in the disease process of DR, yet the molecular mechanisms by which neuroinflammation activation occurs are not fully understood. This study shows that elevated glucose levels enhance O-GlcNAcylation of voltage-dependent anion channel 1 (VDAC1) at threonine 165. This modification promotes VDAC1 oligomerization, facilitating cytosolic translocation of mtDNA. The cytosolic mtDNA activates Z-DNA binding protein 1, leading to its activation and subsequent inflammatory responses. Importantly, mtDNA levels in the vitreous fluid of patients with DR were higher, and mtDNA levels were positively correlated with the retinal thickness and negatively correlated with visual acuity. Taken together, our findings reveal a hyperglycemia-driven signaling axis in M\u00fcller cells that couples metabolic dysregulation with neuroinflammation, offering mechanistic insights and therapeutic opportunities for DR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>The limited efficacy of anti-VEGF therapy in diabetic retinopathy (DR) highlights the importance of nonvascular mechanisms in disease progression. Hyperglycemia is a key driver of neuroinflammation in DR. Hyperglycemia results in VDAC1 O-GlcNAcylation in M\u00fcller glia, leading to mtDNA release and ZBP1 activation, thereby linking metabolic stress to neuroinflammation in DR. Targeting VDAC1-mediated mtDNA release or using vitreous mtDNA as a biomarker may enable earlier diagnosis and novel therapeutic strategies for DR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db26-0151","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:37:30Z","timestamp":1784554650000},"page":"1685-1700","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["VDAC1\n                    <i>O<\/i>\n                    -GlcNAcylation Promotes mtDNA Release and Activates ZBP1-Dependent Neuroinflammation in Diabetic Retinopathy"],"prefix":"10.2337","volume":"75","author":[{"given":"Xin","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University, Wuxi People\u2019s Hospital, Wuxi Medical Center, Nanjing Medical University 1 , Wuxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lipeng","family":"Guan","sequence":"additional","affiliation":[{"name":"Affiliated Huishan Hospital of Xinglin College, Nantong University 2 , Wuxi Huishan District People's Hospital, Wuxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University, Wuxi People\u2019s Hospital, Wuxi Medical Center, Nanjing Medical University 1 , Wuxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Affiliated Wuxi People\u2019s Hospital of Nanjing Medical University, Wuxi People\u2019s Hospital, Wuxi Medical Center, Nanjing Medical University 1 , Wuxi, 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