{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:03:04Z","timestamp":1786122184977,"version":"build-2736575974"},"reference-count":105,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"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":["EY027005"],"award-info":[{"award-number":["EY027005"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"award":["EY027005"],"award-info":[{"award-number":["EY027005"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000928","name":"The Welch Foundation","doi-asserted-by":"publisher","award":["BK-0031"],"award-info":[{"award-number":["BK-0031"]}],"id":[{"id":"10.13039\/100000928","id-type":"DOI","asserted-by":"publisher"}]},{"award":["BK-0031"],"award-info":[{"award-number":["BK-0031"]}],"id":[{"id":"https:\/\/ror.org\/00np6vq88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Neurobiology of Aging and Alzheimer\u2019s Disease Training","award":["NIH T32 AG020494"],"award-info":[{"award-number":["NIH T32 AG020494"]}]},{"award":["NIH T32 AG020494"],"award-info":[{"award-number":["NIH T32 AG020494"]}],"id":[{"id":"https:\/\/ror.org\/04ateak98","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Mass spectrometry-based proteomics has become instrumental for elucidating the molecular mechanisms of neurodegeneration, enabling the identification of disease-associated proteomic alterations and protein-level responses to therapeutic interventions. Building on our previous proteomic characterization of the orchiectomized (ORX) Brown Norway male rat retina as a model of androgen deprivation, we extend this investigation to the visual cortex (VC), a key node in the visual pathway. Here we report the first comprehensive proteomic characterization of ORX-VC employing nanoflow liquid chromatography\u2013tandem mass spectrometry complemented by bioinformatic pathway analyses and quantitative assessment of selected protein markers of ORX-induced changes. Our discovery-driven proteomics approach revealed over 500 differentially expressed proteins following ORX. Principal component analysis showed complete separation between ORX and na\u00efve groups with no overlap, indicating a profound effect of androgen deprivation on the VC proteome. Ingenuity Pathway Analysis\u00ae predicted that the widespread proteome dysregulation included oxidative stress as a primary contributor, alongside estrogen receptor (ESR) predominance over androgen receptor signaling, consistent with our prior findings in the ORX retina. To explore whether this ESR predominance translates to a benefit of E2 supplementation alone, independent of circulating testosterone, we utilized our DHED (10\u03b2,17\u03b2-dihydroxyestra-1,4-dien-3-one) prodrug as eye drops to target E2 formation into the retina. Quantitative assessment demonstrated that this approach resulted in attenuation of ORX-induced expression changes in a selected panel of key proteins. These findings warrant future studies to determine whether this effect extends across the full spectrum of ORX-induced proteomic shifts and confers a benefit for vision preservation.<\/jats:p>","DOI":"10.3390\/antiox15080976","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T13:03:27Z","timestamp":1786021407000},"page":"976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bypassing Androgens: Retina-Targeted 17\u03b2-Estradiol Delivery via DHED Eye Drops Ameliorates Orchiectomy-Induced Shifts in the Male Rat Visual Cortex Proteome"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4876-765X","authenticated-orcid":false,"given":"Khadiza","family":"Zaman","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9795-1109","authenticated-orcid":false,"given":"Ammar","family":"Kapic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5633-842X","authenticated-orcid":false,"given":"Vien","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4559-3458","authenticated-orcid":false,"given":"Laszlo","family":"Prokai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5595-1346","authenticated-orcid":false,"given":"Katalin","family":"Prokai-Tatrai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101628","DOI":"10.1016\/j.smim.2022.101628","article-title":"Pathophysiology of neurodegenerative diseases: An interplay among axonal transport failure, oxidative stress, and inflammation?","volume":"59","author":"Tesco","year":"2022","journal-title":"Semin. 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