PXD059520-1

PXD059520 is an original dataset announced via ProteomeXchange.

Title	Retina-Targeted 17β-Estradiol by the DHED Prodrug Rescues Visual Function and Actuates Neuroprotective Protein Net-works 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 and Andrew J. Feola
Description	The association between 17β-estradiol (E2) deprivation, seen in menopause and a risk for devel-oping 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 outcomes 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 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. Discov-ery-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 re-veals the therapeutic potential of the prodrug to prevent visual deficits after glaucomatous retinal injury.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_06:30:42.909.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD059520
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Laszlo Prokai
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-07 13:22:43	ID requested
⏵ 1	2025-05-07 06:30:43	announced

Prokai-Tatrai K, Zaman K, Kapic A, Hogan K, Sanchez-Rodriguez G, Silverio AE, Nguyen V, Prokai L, Feola AJ, -Estradiol by the DHED Prodrug Rescues Visual Function and Actuates Neuroprotective Protein Networks After Optic Nerve Crush in a Rat Model of Surgical Menopause. Int J Mol Sci, 26(5):(2025) [pubmed]

10.6019/PXD059520;

10.3390/ijms26051846;

submitter keyword: bioinformatics

DHED

estrogen

glaucoma

menopause

optic nerve crush

optomotor response

protein–protein interaction networks

quantitative label-free retina proteomics

Laszlo Prokai, Ph.D., D.Sc
contact affiliation	Professor and Robert A. Welch Chair in Biochemistry Department of Pharmacology and Neuroscience University of North Texas Health Science Center at FortWorth
contact email	laszlo.prokai@unthsc.edu
lab head
Laszlo Prokai
contact affiliation	Department of Pharmacology & Neuroscience UNT Health Science Center Fort Worth, TX, USA
contact email	advancedms@unthsc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059520
     1. Label: PRIDE project
     2. Name: Retina-Targeted 17β-Estradiol by the DHED Prodrug Rescues Visual Function and Actuates Neuroprotective Protein Net-works 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 and Andrew J. Feola