{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T02:51:10Z","timestamp":1788058270684,"version":"build-2784847793"},"reference-count":36,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"Jiangsu Provincial Key Research and Development Programme-social development","award":["BE2023777"],"award-info":[{"award-number":["BE2023777"]}]},{"name":"Key medical research project of Jiangsu Commission of Health","award":["H2022185"],"award-info":[{"award-number":["H2022185"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271100"],"award-info":[{"award-number":["82271100"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Diabetic retinopathy (DR) is a predominant cause of vision impairment among working-age individuals, with a subset of patients responding poorly to current treatments. This study investigated alterations in double-stranded DNA (dsDNA) levels in the aqueous humor and retinal pigment epithelium (RPE) dysfunction in DR patients, exploring the potential role of the cyclic GMP-AMP synthase (cGAS)\u2013STING pathway in DR progression. We found that DR patients showed significantly elevated dsDNA levels in the aqueous humor compared with control individuals. Fundus autofluorescence imaging revealed an increase in high-autofluorescence spots in DR patients, indicating early RPE dysfunction. In vivo and in\u00a0vitro models of DR demonstrated mitochondrial damage and dsDNA leakage in RPE cells, along with cGAS-STING pathway activation in the retina. Pharmacological inhibition of STING reduced cytoplasmic dsDNA accumulation and damaged mitochondria, alleviating inflammation in\u00a0vitro. In vivo, STING inhibition ameliorated RPE dysfunction and vascular changes. These findings highlight the critical role of the cGAS-STING pathway in DR pathogenesis and suggest that STING inhibition may serve as a promising therapeutic strategy to reduce retinal inflammation and slow the progression of DR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>The retinal pigment epithelium (RPE) serves as the outer blood-retinal barrier, protecting the neural retina from systemic changes. We aimed to preserve RPE integrity through early intervention and inhibit DR progression. Our study focused on determining whether the involvement of the cyclic GMP-AMP synthase\u2013STING pathway and mitochondrial damage drive RPE dysfunction. We found that mitochondrial dysfunction in the RPE under diabetic conditions triggers activation of the cyclic GMP-AMP synthase\u2013STING pathway, leading to disruption of RPE and retinal vascular instability. Targeting this pathway restored RPE function and limited retinal deterioration. These findings highlight a promising therapeutic approach for preventing disease progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0128","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:53:34Z","timestamp":1779116014000},"page":"1285-1297","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":2,"title":["cGAS-STING Pathway Mediates Retinal Pigmental Epithelial Dysfunction in Diabetic Retinopathy"],"prefix":"10.2337","volume":"75","author":[{"given":"Zhaoqi","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aowang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyun","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1605-1964","authenticated-orcid":false,"given":"Qinghuai","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University , Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0371-0218","authenticated-orcid":false,"given":"Weiwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University , Nanjing, 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