{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:32:27Z","timestamp":1787027547755,"version":"build-2736575974"},"reference-count":97,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"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"}]},{"name":"the Neurobiology of Aging and Alzheimer\u2019s Disease Training Grant","award":["NIH T32 AG020494"],"award-info":[{"award-number":["NIH T32 AG020494"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Elevated oxidative stress (OS) is a primary driver of ocular neurodegeneration, worsening with age-related declines in gonadal hormones. While the loss of endogenous 17\u03b2-estradiol (E2) is a recognized risk factor for retinal degeneration in females, the impact of testosterone depletion in males remains poorly understood. To address this knowledge gap, we employed mass spectrometry-based proteomics and bioinformatic pipelines to characterize retinal protein shifts triggered by orchiectomy (ORX) in the Brown Norway rat. Proteins from ORX and intact retinas were analyzed via a discovery-driven approach using nanoflow liquid chromatography\u2013tandem mass spectrometry with data-independent acquisition. Ingenuity Pathway Analysis\u00ae of differentially expressed proteins (DEPs) revealed nearly 300 significantly regulated canonical pathways, many associated with OS, free radical detoxification, mitochondrial dysfunction and ophthalmic disease. A selected panel of DEPs was verified by protein-targeted data extraction. Notably, pathway analysis revealed the prominence of estrogen receptor signaling over androgen receptor signaling in the retina, despite the loss of male sex hormones following ORX. These findings indicate that E2-mediated pathways play a more significant role in male retinal protection than previously recognized. Our study provides the first proteomics-based evidence of the male rat retina\u2019s heightened susceptibility to ORX-associated OS, identifying potential targets for treating sex hormone deprivation-associated retinal neurodegeneration.<\/jats:p>","DOI":"10.3390\/antiox15040479","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T10:19:14Z","timestamp":1776075554000},"page":"479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact\u00a0of Orchiectomy on Oxidative Stress-Induced Neurodegeneration in the Male Rat Retina: A Proteomic Analysis"],"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\/0000-0001-5595-1346","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":[[2026,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Marchesi, N., Fahmideh, F., Boschi, F., Pascale, A., and Barbieri, A. 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