Evidence map›Paper›PMID 40076480›Full record

ArticleInternational journal of molecular sciences2025

Retina-Targeted 17β-Estradiol by the DHED Prodrug Rescues Visual Function and Actuates Neuroprotective Protein Networks After Optic Nerve Crush in a Rat Model of Surgical Menopause.

Katalin Prokai-Tatrai, Khadiza Zaman, Ammar Kapic, Kelleigh Hogan, Gabriela Sanchez-Rodriguez, Anna E Silverio, Vien Nguyen, Laszlo Prokai, Andrew J Feola

Abstract read
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Katalin Prokai-TatraiDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.ORCID 0000-0001-5595-1346
Khadiza ZamanDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.ORCID 0000-0003-4876-765X
Ammar KapicDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.ORCID 0000-0001-9795-1109
Kelleigh HoganCenter for Visual and Neurocognitive Rehabilitation, Joseph M. Cleland Atlanta VA Medical Center, Decatur, GA 30033, USA.
Gabriela Sanchez-RodriguezWallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
Anna E SilverioDepartment of Ophthalmology, Emory Eye Center, School of Medicine, Emory University, Atlanta, GA 30322, USA.
Vien NguyenDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.ORCID 0009-0004-5633-842X
Laszlo ProkaiDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.ORCID 0000-0002-4559-3458
Andrew J FeolaCenter for Visual and Neurocognitive Rehabilitation, Joseph M. Cleland Atlanta VA Medical Center, Decatur, GA 30033, USA.

Funding

P30-Core Grant for Vision Research Core CP30EY006360 · NEI · EMORY UNIVERSITY · PI BOATRIGHT, JEFFREY H · 1986 to 2025
$15.3M
Training in the Neurobiology of Aging and Alzheimer's DiseaseT32AG020494 · NIA · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI ROBERT Clinton BARBER, NATHALIE SUMIEN · 2002 to 2026
$6.9M
A Novel Neuroprotective Approach for GlaucomaR01EY027005 · NEI · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI KATALIN T PROKAI · 2016 to 2026
$3.9M
Impact of Menopause on the Aqueous Outflow PathwayR01EY030871 · NEI · GEORGIA INSTITUTE OF TECHNOLOGY · PI FEOLA, ANDREW J · 2020 to 2024
$1.6M
Assessing the Impact of Age, Sex, and Menopause on Scleral Biomechanics and Gene ExpressionR21EY035468 · NEI · EMORY UNIVERSITY · PI FEOLA, ANDREW J · 2023 to 2023
$438k
Department of Veterans Affairs Rehab R&D Service Career Development Awards RX002342"La Caixa" Foundation Fellowship 100010434 - LCF/BQ/EU21/11890105NEI NIH HHS P30 EY006360NEI NIH HHS R01 EY027005NEI NIH HHS R01 EY030871NEI NIH HHS R21 EY035468NIA NIH HHS T32 AG020494NIH HHS 2R01EY027005-07X1NIH HHS EY030871NIH HHS EY035468NIH HHS P30 EY06360NIH HHS T32 AG02049Robert A. Welch Foundation BK-0031RRD VA IK2 RX002342
6 · The paper itself

Abstract

The association between 17β-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 10β,17β-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.

Indexed as

EstradiolMenopauseNeuroprotective AgentsOptic Nerve InjuriesProdrugsRetinaAnimalsDisease Models, AnimalFemaleGlaucomaNerve CrushOptic NerveOvariectomyProteomicsRatsRetinal Ganglion CellsEstradiolNeuroprotective AgentsProdrugsbioinformaticsDHEDestrogenglaucomamenopauseoptic nerve crushoptomotor responseprotein–protein interaction networksquantitative label-free retina proteomics

Identifiers

PMID40076480
PMCPMC11899211

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.