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

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Retina

DISEASE(S): Glaucoma

SUBMITTER: Laszlo Prokai  

LAB HEAD: Laszlo Prokai, Ph.D., D.Sc

PROVIDER: PXD059520 | Pride | 2025-05-07

REPOSITORIES: Pride