{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:25:56Z","timestamp":1792790756072,"version":"4.5.0"},"reference-count":63,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":224,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003996","name":"Kunming Medical University","doi-asserted-by":"publisher","award":["202201AY070001-264"],"award-info":[{"award-number":["202201AY070001-264"]}],"id":[{"id":"10.13039\/501100003996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003996","name":"Kunming Medical University","doi-asserted-by":"publisher","award":["202301AY070001-140"],"award-info":[{"award-number":["202301AY070001-140"]}],"id":[{"id":"10.13039\/501100003996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008871","name":"Yunnan Provincial Science and Technology Department","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460210"],"award-info":[{"award-number":["82460210"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    Diabetic retinopathy (DR), a leading cause of vision impairment worldwide, is characterized by early neuronal damage in the retina, termed diabetic neuropathy in the retina (DNR). This condition is marked by neuronal apoptosis and glial activation. M\u00fcller glia are retinal cells highly susceptible to diabetic metabolic stress that may undergo ferroptosis, an iron\u2010dependent form of regulated cell death driven by lipid peroxidation. However, the role of ferroptosis in DNR pathogenesis remains undefined. In this study, we investigated M\u00fcller cell injury under high\u2010glucose and palmitic acid (HGP) conditions. The retinal tissues were obtained from normal rabbits and alloxan\u2010induced diabetic rabbits. HGP exposure significantly reduced M\u00fcller cell viability, induced cell cycle arrest, and elevated proinflammatory cytokines. Ultrastructural analysis revealed mitochondrial damage, accompanied by decreased glutathione (GSH) and increased malondialdehyde (MDA), ferrous iron (Fe\n                    <jats:sup>2+<\/jats:sup>\n                    ), and reactive oxygen species (ROS) levels. RNA sequencing (RNA\u2010Seq) identified\n                    <jats:italic>SQSTM1<\/jats:italic>\n                    as a ferroptosis\u2010related differentially expressed gene, which was significantly upregulated in HGP\u2010treated cells. In vivo, DNR rabbits exhibited oxidative stress, iron dysregulation, and elevated SQSTM1 expression that colocalized with GFAP\n                    <jats:sup>+<\/jats:sup>\n                    M\u00fcller cells. Single\u2010cell RNA\u2010Seq of human proliferative diabetic retinopathy (PDR) retinas confirmed elevated SQSTM1 expression in M\u00fcller cells compared to healthy control (HC) retinas. Mechanistically,\n                    <jats:italic>SQSTM1<\/jats:italic>\n                    knockdown attenuated ferroptosis, oxidative stress, and HGP\u2010induced injury, while its overexpression exacerbated ferroptosis via ACSL4 upregulation. Overall, our findings suggest that SQSTM1 may serve as a critical mediator linking M\u00fcller cell dysfunction and ferroptosis in DNR pathogenesis, offering a novel potential therapeutic target.\n                  <\/jats:p>","DOI":"10.1155\/jdr\/1924668","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T17:34:12Z","timestamp":1755106452000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Upregulation of SQSTM1 Regulates Ferroptosis and Oxidative Stress in M\u00fcller Cells of the Diabetic Neural Retina by Modulating ACSL4"],"prefix":"10.1155","volume":"2025","author":[{"given":"Xinlu","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bai","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Defei","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binyang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaiyan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9081-7400","authenticated-orcid":false,"given":"Xiaojing","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2893-0096","authenticated-orcid":false,"given":"Ninghua","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2128-1967","authenticated-orcid":false,"given":"Yan","family":"Mei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2021.1984535"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2020.100919"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032927"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3723"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-07180-8"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202100334"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkad051"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115895"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2024.114087"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102292"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.05.003"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-020-00789-5"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2025.110299"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-024-04496-8"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114978"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.9960"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1659612"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113631"},{"key":"e_1_2_13_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063315"},{"key":"e_1_2_13_20_2","doi-asserted-by":"publisher","DOI":"10.31083\/FBL27954"},{"key":"e_1_2_13_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2020.01.005"},{"key":"e_1_2_13_22_2","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/1470898"},{"key":"e_1_2_13_23_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2015-306719"},{"key":"e_1_2_13_24_2","doi-asserted-by":"publisher","DOI":"10.1177\/0962280209351925"},{"key":"e_1_2_13_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl4896"},{"key":"e_1_2_13_26_2","doi-asserted-by":"publisher","DOI":"10.2337\/db21-0551"},{"key":"e_1_2_13_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-022-00947-2"},{"key":"e_1_2_13_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155293"},{"key":"e_1_2_13_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.862702"},{"key":"e_1_2_13_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106516"},{"key":"e_1_2_13_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-01141-y"},{"key":"e_1_2_13_32_2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.355743"},{"key":"e_1_2_13_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-024-01847-y"},{"key":"e_1_2_13_34_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11233756"},{"key":"e_1_2_13_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03021-x"},{"key":"e_1_2_13_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2112561118"},{"key":"e_1_2_13_37_2","doi-asserted-by":"publisher","DOI":"10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