{
    "abstract": "The association between 17\u03b2-estradiol (E2) deprivation, seen in menopause, and a risk for developing glaucoma has been shown. Thus, exogenous supplementation of E2 may protect against retinal ganglion cell (RGC) degradation and vision loss. Here, we investigated the utility of topical 10\u03b2,17\u03b2-dihydroxyestra-1,4-dien-3-one (DHED), a prodrug of E2 that selectively produces the neuroprotective hormone in the retina, on visual function after optic nerve crush (ONC) and ovariectomy (OVX). We used female Brown Norway rats that underwent either Sham or OVX surgeries. After ONC, OVX animals received DHED or vehicle eye drops for 12 weeks. Visual function, via the optomotor reflex, and retinal thickness, via optical coherence tomography, were followed longitudinally. Afterward, we performed mass spectrometry-based label-free retina proteomics to survey retinal protein interaction networks in our selected animal model and to identify E2-responsive proteins after OVX on neurodegeneration. We found that ONC with OVX caused a significant decline in visual functions that were ameliorated by DHED treatments. Discovery-driven retina proteomics identified numerous proteins associated with neurodegenerative processes due to ONC that were remediated by DHED eye drops. Altogether, our three-pronged phenotypic preclinical evaluation of the topical DHED in the OVX + ONC model of glaucoma reveals the therapeutic potential of the prodrug to prevent visual deficits after glaucomatous retinal injury.",
    "authors": [
        {
            "affiliation": "Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.",
            "firstname": "Katalin",
            "initials": "K",
            "lastname": "Prokai-Tatrai"
        },
        {
            "affiliation": "Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.",
            "firstname": "Khadiza",
            "initials": "K",
            "lastname": "Zaman"
        },
        {
            "affiliation": "Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.",
            "firstname": "Ammar",
            "initials": "A",
            "lastname": "Kapic"
        },
        {
            "affiliation": "Center for Visual and Neurocognitive Rehabilitation, Joseph M. Cleland Atlanta VA Medical Center, Decatur, GA 30033, USA.\nWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.\nDepartment of Ophthalmology, Emory Eye Center, School of Medicine, Emory University, Atlanta, GA 30322, USA.",
            "firstname": "Kelleigh",
            "initials": "K",
            "lastname": "Hogan"
        },
        {
            "affiliation": "Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.\nDepartment of Ophthalmology, Emory Eye Center, School of Medicine, Emory University, Atlanta, GA 30322, USA.\nDepartment of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA 30322, USA.",
            "firstname": "Gabriela",
            "initials": "G",
            "lastname": "Sanchez-Rodriguez"
        },
        {
            "affiliation": "Department of Ophthalmology, Emory Eye Center, School of Medicine, Emory University, Atlanta, GA 30322, USA.",
            "firstname": "Anna E",
            "initials": "AE",
            "lastname": "Silverio"
        },
        {
            "affiliation": "Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.",
            "firstname": "Vien",
            "initials": "V",
            "lastname": "Nguyen"
        },
        {
            "affiliation": "Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.",
            "firstname": "Laszlo",
            "initials": "L",
            "lastname": "Prokai"
        },
        {
            "affiliation": "Center for Visual and Neurocognitive Rehabilitation, Joseph M. Cleland Atlanta VA Medical Center, Decatur, GA 30033, USA.\nWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.\nDepartment of Ophthalmology, Emory Eye Center, School of Medicine, Emory University, Atlanta, GA 30322, USA.",
            "firstname": "Andrew J",
            "initials": "AJ",
            "lastname": "Feola"
        }
    ],
    "conclusions": null,
    "copyrights": null,
    "doi": "10.3390/ijms26051846\n10.1016/bs.ctdb.2016.12.005\n10.1016/j.neubiorev.2021.12.007\n10.1016/j.yfrne.2021.100926\n10.1124/pr.109.002071\n10.1016/j.neulet.2021.135849\n10.1016/bs.pmbts.2018.07.008\n10.1210/er.20.3.279\n10.2147/NAN.S105134\n10.1007/s12035-016-0198-3\n10.4103/1673-5374.219036\n10.1146/annurev.physiol.66.032802.154945\n10.1016/S0165-0173(01)00136-9\n10.1515/revneuro-2015-0032\n10.1016/S0079-6123(08)01144-8\n10.1007/s00417-014-2771-7\n10.1111/j.1582-4934.2010.01010.x\n10.1155/2013/563481\n10.1016/j.yfrne.2010.12.005\n10.31887/DCNS.2002.4.2/ddubal\n10.1158/1055-9965.EPI-24-0577\n10.1002/rth2.12763\n10.1152/physrev.00018.2016\n10.3390/molecules24224197\n10.1016/j.ophtha.2010.09.002\n10.3390/cells9030535\n10.1016/j.mam.2023.101193\n10.1097/WCO.0000000000000777\n10.1111/j.1442-9071.2011.02563.x\n10.1016/j.ajoint.2024.100013\n10.1097/gme.0b013e3182443137\n10.1016/j.exer.2019.107706\n10.3390/cells11193062\n10.1007/s10571-021-01179-z\n10.1016/j.exer.2020.108333\n10.1021/mp400313u\n10.1016/j.steroids.2015.08.002\n10.3390/pharmaceutics12050456\n10.3390/pharmaceutics13091392\n10.1006/exer.1996.0184\n10.3390/cells13131126\n10.3390/ijms241612592\n10.1038/s41598-020-71460-6\n10.3389/fcell.2022.956279\n10.3389/fpsyt.2024.1408878\n10.1016/S0042-6989(00)00081-X\n10.1016/j.omtn.2023.02.029\n10.3791/2685-v\n10.1167/tvst.10.1.22\n10.1167/iovs.63.8.3\n10.1038/s41594-019-0332-9\n10.1038/sj.cdd.4401384\n10.3389/fncel.2024.1379540\n10.1007/s00417-012-2157-7\n10.1371/journal.pone.0049730\n10.1167/iovs.05-0767\n10.1074/mcp.M600245-MCP200\n10.1007/s12031-011-9537-z\n10.1111/jnc.13902\n10.3390/ijms24021206\n10.1097/IJG.0000000000000553\n10.1038/s41419-018-1041-8\n10.3390/ijms21207777\n10.1016/j.yfrne.2006.09.004\n10.1038/cr.2009.139\n10.1089/089771503322385827\n10.1038/s41586-023-06935-3\n10.1007/s00401-021-02366-4\n10.1016/j.exer.2008.04.012\n10.1073/pnas.1608769114\n10.1093/hmg/ddaa209\n10.1016/j.neuroscience.2013.08.023\n10.1084/jem.20160412\n10.1186/s12974-016-0558-y\n10.1007/s00424-021-02562-x\n10.1038/s41598-018-20893-1\n10.1016/j.celrep.2016.05.012\n10.3390/ijms23115977\n10.1523/JNEUROSCI.2994-19.2020\n10.1002/ajmg.c.32045\n10.3389/fnins.2023.1132179\n10.1126/scitranslmed.aau6627\n10.1167/iovs.13-12771\n10.1016/S1350-9462(02)00043-5\n10.1073/pnas.200377097\n10.1038/nrn3670\n10.3390/ijms20102563\n10.3390/ijms22147581\n10.1126/scitranslmed.aab1290\n10.3892/etm.2012.619\n10.1017/S0952523805225166\n10.3390/pharmaceutics12020101\n10.1021/ac0341261\n10.1021/pr0600273\n10.1038/nbt.2839",
    "journal": "International journal of molecular sciences",
    "keywords": [
        "DHED",
        "bioinformatics",
        "estrogen",
        "glaucoma",
        "menopause",
        "optic nerve crush",
        "optomotor response",
        "protein\u2013protein interaction networks",
        "quantitative label-free retina proteomics"
    ],
    "methods": null,
    "publication_date": "2025-03-13",
    "pubmed_id": "40076480\n28527569\n34890602\n34089761\n20392807\n33775739\n30470289\n10368772\n28845391\n27822715\n29239320\n14977405\n11744096\n26461840\n18929136\n25216739\n20070435\n26316993\n21163293\n22034440\n39190182\n36032216\n28539434\n31752337\n21126771\n32106630\n37331129\n31809331\n22697056\n22415565\n31226338\n36231022\n34981287\n33129829\n23841874\n26265586\n32429388\n34575465\n9093024\n38994978\n37628770\n33060618\n36035999\n39081530\n10878281\n36950280\n21540827\n33510961\n35816047\n31792453\n14752512\n39318470\n23073841\n23468831\n16303980\n17264069\n21584655\n27859240\n36674721\n27755351\n30258047\n33096634\n17055560\n20010915\n14577867\n38086421\n34487221\n18572163\n28446616\n32959884\n23988434\n28416649\n27126275\n33860373\n29440717\n27239031\n35682657\n32265257\n37212526\n37077319\n31270273\n24168994\n12597922\n10995484\n24552784\n31137749\n34299211\n26203081\n23181107\n16332278\n32012756\n14632076\n17081042\n24727771",
    "results": null,
    "title": "Retina-Targeted 17\u03b2-Estradiol by the DHED Prodrug Rescues Visual Function and Actuates Neuroprotective Protein Networks After Optic Nerve Crush in a Rat Model of Surgical Menopause.",
    "xml": "<Element 'PubmedArticle' at 0x78850458f0b0>"
}