{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:47:32Z","timestamp":1779889652208,"version":"3.53.1"},"reference-count":74,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T00:00:00Z","timestamp":1621900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY027013 [ M.R.B.],  R01EY020825 [A.S.L]; R01EY026268 [A.S.L]."],"award-info":[{"award-number":["EY027013 [ M.R.B.],  R01EY020825 [A.S.L]; R01EY026268 [A.S.L]."]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008900","name":"University of South Florida","doi-asserted-by":"publisher","award":["Start up [M.R.B.]"],"award-info":[{"award-number":["Start up [M.R.B.]"]}],"id":[{"id":"10.13039\/100008900","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Erythropoietin (EPO) plays an important role in erythropoiesis by its action in blocking apoptosis of progenitor cells and protects both photoreceptors and retinal ganglion cells from induced or inherited degeneration. A modified form of EPO, EPO-R76E has attenuated erythropoietic activity but is effective in inhibiting apoptosis, oxidative stress, and inflammation in several models of retinal degeneration. In this study, we used recombinant Adeno Associated Virus (AAV) to provide long-term sustained delivery of EPO-R76E and demonstrated its effects in a mouse model of dry-AMD in which retinal degeneration is induced by oxidative stress in the retinal pigment epithelial (RPE) cells. Experimental vector AAV-EPO-R76E and control vector AAV-GFP were packaged into serotype-1 (AAV1) to enable RPE selective expression. RPE oxidative stress-mediated retinal degeneration was induced by exon specific deletion of the protective enzyme MnSOD (encoded by Sod2) by cre\/lox mechanism. Experimental mice received subretinal injection of AAV-EPO-R76E in the right eye and AAV-GFP in the left eye. Western blotting of RPE\/choroid protein samples from AAV-EPO-R76E injected eyes showed RPE specific EPO expression. Retinal function was monitored by electroretinography (ERG). EPO-R76E over-expression in RPE delayed the retinal degeneration as measured by light microscopy in RPE specific Sod2 knockout mice. Delivery of EPO-R76E vector can be used as a tool to prevent retinal degeneration induced by RPE oxidative stress, which is implicated as a potential cause of Age-Related Macular Degeneration.<\/jats:p>","DOI":"10.3390\/antiox10060842","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T13:14:21Z","timestamp":1621948461000},"page":"842","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Erythropoietin Gene Therapy Delays Retinal Degeneration Resulting from Oxidative Stress in the Retinal Pigment Epithelium"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9685-2923","authenticated-orcid":false,"given":"Manas R.","family":"Biswal","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"},{"name":"Department of Ophthalmology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"},{"name":"Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"},{"name":"Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Ophthalmology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan J.","family":"Paulson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rukshana R.","family":"Uddin","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Chemistry, University of Florida, Gainesville, FL 32603, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4132-5640","authenticated-orcid":false,"given":"Yao","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Cell & Molecular Biology, Tulane University, New Orleans, LA 70118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Florida College of Medicine, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4192-9727","authenticated-orcid":false,"given":"Alfred S.","family":"Lewin","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA"},{"name":"Department of Ophthalmology, University of Florida College of Medicine, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1001\/archopht.122.4.564","article-title":"Eye Diseases Prevalence Research Group Prevalence of Age-Related Macular Degeneration in the United States","volume":"122","author":"Friedman","year":"2004","journal-title":"Arch. 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