{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T04:39:35Z","timestamp":1769575175275,"version":"3.49.0"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Diabetic retinopathy (DR) is a major complication of diabetes mellitus. Growing evidence shows that hyperglycemia causes not only microvascular damage but also retinal neural dysfunction. Although different metabolic pathways have been implicated, the exact mechanism behind retinal degeneration remains unclear. Hyperglycemic stimuli have been shown to reduce the function of the retinal blood\u2013barrier (BRB) in both diabetic humans and animals. As part of the BRB, the retinal pigment epithelium (RPE) plays a key role in retinal function by regulating the flow of metabolites and ions between the choroidal blood supply and the outer retina, and by supporting photoreceptor cell functions. Therefore, RPE dysfunction can lead to retinal injury. To understand the role of RPE in DR, we studied oxidative stress in the RPE at the early onset of streptozotocin\u2010induced diabetes in rats. We found a 60% increase in lipoperoxidation at 45\u2009days of diabetes, along with a 50% reduction in ascorbic acid content. Oxidized proteins were significantly increased after 20 and 45\u2009days of diabetes induction, and changes in cell\u2013cell contacts were observed. Despite these findings, superoxide dismutase activity was greatly increased at 45\u2009days of diabetes, while Nrf2 expression and levels of total and reduced glutathione, key regulators of cellular antioxidant capacity, were similar in control and diabetic rat RPE. Moreover, the increase in oxidized proteins was not affected by the antioxidant quercetin nor by the NOS inhibitor L\u2010NAME. These findings suggest that protein carbonylation may impair protein function or turnover, which in turn leads to RPE damage.<\/jats:p>","DOI":"10.1096\/fba.2025-00230","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T07:34:47Z","timestamp":1769067287000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diabetes Induces Accumulation of Carbonylated Proteins in the Rat Retinal Pigment Epithelium Independently of Oxidative Stress"],"prefix":"10.1096","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6778-7017","authenticated-orcid":false,"given":"Elena","family":"Morales\u2010Ram\u00edrez","sequence":"first","affiliation":[{"name":"Departamento de Neurodesarrollo y Fisiolog\u00eda, Instituto de Fisiolog\u00eda Celular Universidad Nacional Aut\u00f3noma de M\u00e9xico  Ciudad de M\u00e9xico M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5279-8590","authenticated-orcid":false,"given":"Juan David","family":"Villeda\u2010Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Departamento de Neurodesarrollo y Fisiolog\u00eda, Instituto de Fisiolog\u00eda Celular Universidad Nacional Aut\u00f3noma de M\u00e9xico  Ciudad de M\u00e9xico M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1331-9358","authenticated-orcid":false,"given":"Gustavo","family":"S\u00e1nchez\u2010Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Departamento de Neurodesarrollo y Fisiolog\u00eda, Instituto de Fisiolog\u00eda Celular Universidad Nacional Aut\u00f3noma de M\u00e9xico  Ciudad de M\u00e9xico M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7882-6385","authenticated-orcid":false,"given":"Roc\u00edo","family":"Salceda","sequence":"additional","affiliation":[{"name":"Departamento de Neurodesarrollo y Fisiolog\u00eda, Instituto de Fisiolog\u00eda Celular Universidad Nacional Aut\u00f3noma de M\u00e9xico  Ciudad de M\u00e9xico M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2023.2289"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(80)90055-X"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.74.7.388"},{"key":"e_1_2_10_5_1","first-page":"2408","article-title":"VEGF\u2010Initiated Blood\u2010Retinal Barrier Breakdown in Early Diabetes","volume":"42","author":"Qaum T.","year":"2001","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.08.022"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s592-001-8076-6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2003.08.018"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101799"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2023.109650"},{"key":"e_1_2_10_11_1","article-title":"Targeting Oxidative Stress in Diabetic Retinopathy: Mechanisms, Pathology, and Novel Treatment Approaches","volume":"16","author":"He W.","year":"2025","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.5301\/EJO.2010.6049"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16330"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1569-2590(05)10009-3"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/190724"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.100803"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2017.02.013"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-008-9641-9"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9583-7"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(84)05043-6"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-015-1798-4"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(79)62181-X"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(78)90479-4"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.378"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(61)90170-9"},{"key":"e_1_2_10_26_1","first-page":"2157","article-title":"Angiotensin\u2010Converting Enzyme Activity in Retinas of Streptozotocin\u2010 Induced and Zucker Diabetic Rats: The Effect of Angiotensin II on Na+,K+\u2010ATPase Activity","volume":"37","author":"Ottlecz A.","year":"1996","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4754"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874467214666210420111232"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.13579"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28165961"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2014.06.009"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115680266330678240821060623"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2017.04.010"},{"key":"e_1_2_10_34_1","first-page":"248","article-title":"Effects of the Vegetable Polyphenols Epigallocatechin\u20103\u2010Gallate, Luteolin, Apigenin, Myricetin, Quercetin, and Cyanidin in Primary Cultures of Human Retinal Pigment Epithelial Cells","volume":"20","author":"Chen R.","year":"2014","journal-title":"Molecular Vision"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00814-3"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.12506"},{"key":"e_1_2_10_37_1","volume-title":"Perspectives in Vision Research","author":"Berman E. R.","year":"1991"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.16.6377"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13091291"},{"key":"e_1_2_10_40_1","first-page":"827","article-title":"Reduced and Oxidized Ascorbates in Guinea Pig Retina Under Normal and Light\u2010Exposed Conditions","volume":"24","author":"Woodford B. J.","year":"1983","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_10_41_1","first-page":"1580","article-title":"The Protective Effect of Ascorbate in Retinal Light Damage of Rats","volume":"26","author":"Organisciak D. T.","year":"1985","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpc.2007.02.015"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4835(86)80027-6"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.29.2148"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.01.012"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-005-9236-7"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(86)90184-8"},{"key":"e_1_2_10_48_1","first-page":"702","article-title":"The Effect of Induced Diabetes on the Electroretinogram Components of the Pigmented Rat","volume":"19","author":"Pautler E. L.","year":"1980","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12122129"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.04.007"},{"key":"e_1_2_10_51_1","first-page":"78","article-title":"Functional Characterization of 58\u2010Kilodalton Inhibitor of Protein Kinase in Protecting Against Diabetic Retinopathy via the Endoplasmic Reticulum Stress Pathway","volume":"17","author":"Yang H.","year":"2011","journal-title":"Molecular Vision"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2014.04.015"}],"container-title":["FASEB BioAdvances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fba.2025-00230","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fba.2025-00230","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fba.2025-00230","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T16:11:30Z","timestamp":1769530290000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fba.2025-00230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":51,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1096\/fba.2025-00230"],"URL":"https:\/\/doi.org\/10.1096\/fba.2025-00230","archive":["Portico"],"relation":{},"ISSN":["2573-9832","2573-9832"],"issn-type":[{"value":"2573-9832","type":"print"},{"value":"2573-9832","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-09-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70067"}}