{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:26:33Z","timestamp":1780590393018,"version":"3.54.1"},"reference-count":65,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["R01-EY11766"],"award-info":[{"award-number":["R01-EY11766"]}]},{"name":"National Institute of Health","award":["P30EY031631"],"award-info":[{"award-number":["P30EY031631"]}]},{"name":"Culver Vision Discovery Institute at Augusta University","award":["R01-EY11766"],"award-info":[{"award-number":["R01-EY11766"]}]},{"name":"Culver Vision Discovery Institute at Augusta University","award":["P30EY031631"],"award-info":[{"award-number":["P30EY031631"]}]},{"name":"NIH","award":["R01-EY11766"],"award-info":[{"award-number":["R01-EY11766"]}]},{"name":"NIH","award":["P30EY031631"],"award-info":[{"award-number":["P30EY031631"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Diabetic retinopathy (DR) is a serious complication of diabetes that results from sustained hyperglycemia, hyperlipidemia, and oxidative stress. Under these conditions, inducible nitric oxide synthase (iNOS) expression is upregulated in the macrophages (M\u03a6) and microglia, resulting in increased production of reactive oxygen species (ROS) and inflammatory cytokines, which contribute to disease progression. Arginase 1 (Arg1) is a ureohydrolase that competes with iNOS for their common substrate, L-arginine. We hypothesized that the administration of a stable form of Arg1 would deplete L-arginine\u2019s availability for iNOS, thus decreasing inflammation and oxidative stress in the retina. Using an obese Type 2 diabetic (T2DM) db\/db mouse, this study characterized DR in this model and determined if systemic treatment with pegylated Arg1 (PEG-Arg1) altered the progression of DR. PEG-Arg1 treatment of db\/db mice thrice weekly for two weeks improved visual function compared with untreated db\/db controls. Retinal expression of inflammatory factors (iNOS, IL-1\u03b2, TNF-\u03b1, IL-6) was significantly increased in the untreated db\/db mice compared with the lean littermate controls. The increased retinal inflammatory and oxidative stress markers in db\/db mice were suppressed with PEG-Arg1 treatment. Additionally, PEG-Arg1 treatment restored the blood\u2013retinal barrier (BRB) function, as evidenced by the decreased tissue albumin extravasation and an improved endothelial ZO-1 tight junction integrity compared with untreated db\/db mice.<\/jats:p>","DOI":"10.3390\/cells11182890","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T03:48:04Z","timestamp":1663300084000},"page":"2890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Systemic Administration of Pegylated Arginase-1 Attenuates the Progression of Diabetic Retinopathy"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6120-1231","authenticated-orcid":false,"given":"Ammar A.","family":"Abdelrahman","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5277-441X","authenticated-orcid":false,"given":"Katharine L.","family":"Bunch","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Porsche V.","family":"Sandow","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul N-M","family":"Cheng","sequence":"additional","affiliation":[{"name":"Bio-Cancer Treatment International, Bioinformatics Building, Hong Kong Science Park, Tai Po, Hong Kong SAR 511513, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth B.","family":"Caldwell","sequence":"additional","affiliation":[{"name":"Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Cell Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. William","family":"Caldwell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"Culver Vision Discovery Institute, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e93751","DOI":"10.1172\/jci.insight.93751","article-title":"Diabetic retinopathy: Current understanding, mechanisms, and treatment strategies","volume":"2","author":"Duh","year":"2017","journal-title":"JCI Insight"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ajpath.2016.08.022","article-title":"Mechanistic Insights into Pathological Changes in the Diabetic Retina","volume":"187","author":"Roy","year":"2016","journal-title":"Am. J. 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