{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:16:45Z","timestamp":1788171405034,"version":"build-2803163510"},"reference-count":54,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000971","name":"Diabetes Australia","doi-asserted-by":"publisher","award":["DAP-Y2600026"],"award-info":[{"award-number":["DAP-Y2600026"]}],"id":[{"id":"10.13039\/501100000971","id-type":"DOI","asserted-by":"publisher"}]},{"award":["DAP-Y2600026"],"award-info":[{"award-number":["DAP-Y2600026"]}],"id":[{"id":"https:\/\/ror.org\/008aaf926","id-type":"ROR","asserted-by":"publisher"}]},{"name":"SERTF-Wishlist"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Diabetic retinopathy (DR) is a major cause of preventable visual impairment and develops through intertwined metabolic, oxidative, inflammatory, and neurovascular disturbances. This review examines how chronic hyperglycaemia disrupts retinal glucose handling and redox homeostasis, with particular emphasis on glycogen metabolism as an underappreciated contributor to disease progression. Pathological glycogen accumulation in retinal amacrine cells and the retinal pigment epithelium may arise through altered glycogen synthase localisation and glucose-6-phosphate-dependent activation, potentially disturbing intracellular trafficking and cellular energy balance. These metabolic changes converge with mitochondrial electron transport chain dysfunction, NADPH oxidase activation, polyol pathway flux, and light-driven lipid peroxidation to increase reactive oxygen species generation. At the same time, transient suppression of Nrf2-dependent antioxidant defences, TXNIP-NLRP3 inflammasome signalling, ferroptotic injury, and VEGF-associated oxidative feedback promote blood\u2013retinal barrier breakdown and persistent neuroinflammation. We propose that dysregulated glycogen metabolism and impaired antioxidant capacity form an integrated metabolic\u2013redox network that helps explain cell-specific vulnerability and metabolic memory in DR. Targeting multiple nodes within this network may support earlier, disease-modifying strategies beyond treatment of advanced vascular complications.<\/jats:p>","DOI":"10.3390\/antiox15091093","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:21:19Z","timestamp":1788168079000},"page":"1093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Dysregulation and Oxidative Stress in Diabetic Retinopathy: Glycogen Metabolism, Mitochondrial Dysfunction, and Antioxidant Defences"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6535-8531","authenticated-orcid":false,"given":"Vinuka","family":"De Silva","sequence":"first","affiliation":[{"name":"Centre for Bioinnovation and School of Health, University of the Sunshine Coast, Sippy Downs, QLD 4556, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lochlan J.","family":"Fennell","sequence":"additional","affiliation":[{"name":"Centre for Bioinnovation and School of Health, University of the Sunshine Coast, Sippy Downs, QLD 4556, Australia"},{"name":"Sunshine Coast Health Institute, Birtinya, QLD 4575, Australia"},{"name":"School of Pharmacy and Medicine, Griffith University, Gold Coast, QLD 4215, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell A.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Centre for Bioinnovation and School of Health, University of the Sunshine Coast, Sippy Downs, QLD 4556, Australia"},{"name":"Sunshine Coast Health Institute, Birtinya, QLD 4575, Australia"},{"name":"Mater Research Institute, The University of Queensland, TRI, Brisbane, QLD 4102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s13167-023-00314-8","article-title":"Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications-risks and mitigation","volume":"14","author":"Kropp","year":"2023","journal-title":"EPMA J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"343560","DOI":"10.1155\/2013\/343560","article-title":"Pathophysiology of diabetic retinopathy","volume":"2013","author":"Tarr","year":"2013","journal-title":"ISRN Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"801269","DOI":"10.1155\/2014\/801269","article-title":"Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets","volume":"2014","author":"Safi","year":"2014","journal-title":"BioMed Res. 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