The Prodrug DHED Delivers 17beta-Estradiol into the Retina for Protection of Retinal Ganglion Cells and Preservation of Visual Function in an Animal Model of Glaucoma

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dc.creatorKapic, Ammar
dc.creatorZaman, Khadiza
dc.creatorNguyen, Vien
dc.creatorNeagu, George C.
dc.creatorSumien, Nathalie
dc.creatorProkai, Laszlo
dc.creatorProkai-Tatrai, Katalin
dc.creator.orcid0000-0001-5595-1346 (Prokai-Tatrai, Katalin)
dc.creator.orcid0000-0002-4559-3458 (Prokai, Laszlo)
dc.creator.orcid0000-0002-0077-9873 (Sumien, Nathalie)
dc.date.accessioned2024-07-24T19:45:06Z
dc.date.available2024-07-24T19:45:06Z
dc.date.issued2024-06-29
dc.description.abstractWe report a three-pronged phenotypic evaluation of the bioprecursor prodrug 10beta,17beta-dihydroxyestra-1,4-dien-3-one (DHED) that selectively produces 17beta-estradiol (E2) in the retina after topical administration and halts glaucomatous neurodegeneration in a male rat model of the disease. Ocular hypertension (OHT) was induced by hyperosmotic saline injection into an episcleral vein of the eye. Animals received daily DHED eye drops for 12 weeks. Deterioration of visual acuity and contrast sensitivity by OHT in these animals were markedly prevented by the DHED-derived E2 with concomitant preservation of retinal ganglion cells and their axons. In addition, we utilized targeted retina proteomics and a previously established panel of proteins as preclinical biomarkers in the context of OHT-induced neurodegeneration as a characteristic process of the disease. The prodrug treatment provided retina-targeted remediation against the glaucomatous dysregulations of these surrogate endpoints without increasing circulating E2 levels. Collectively, the demonstrated significant neuroprotective effect by the DHED-derived E2 in the selected animal model of glaucoma supports the translational potential of our presented ocular neuroprotective approach owing to its inherent therapeutic safety and efficacy.
dc.description.sponsorshipThis work was supported by the National Eye Institute (National Institutes of Health (NIH), Bethesda, MD, USA, grant number EY027005 (K.P.-T.) and by the Robert A. Welch Foundation (endowment BK-0031 to L.P.). A.K. was also supported by the Neurobiology of Aging and Alzheimer's Disease Training Grant (NIH T32 AG020494 to N.S.).
dc.identifier.citationKapic, A., Zaman, K., Nguyen, V., Neagu, G. C., Sumien, N., Prokai, L., & Prokai-Tatrai, K. (2024). The Prodrug DHED Delivers 17β-Estradiol into the Retina for Protection of Retinal Ganglion Cells and Preservation of Visual Function in an Animal Model of Glaucoma. Cells, 13(13), 1126. https://doi.org/10.3390/cells13131126
dc.identifier.issn2073-4409
dc.identifier.issue13
dc.identifier.urihttps://hdl.handle.net/20.500.12503/32877
dc.identifier.volume13
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/cells13131126
dc.rights.holder© 2024 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0 Deed)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceCells
dc.subject17beta-estradiol
dc.subjectDHED
dc.subjectcontrast sensitivity
dc.subjectglaucoma
dc.subjectneuroprotection
dc.subjectoptomotor response
dc.subjectretina proteomics
dc.subjectvisual acuity
dc.subject.meshRetinal Ganglion Cells / drug effects
dc.subject.meshRetinal Ganglion Cells / pathology
dc.subject.meshRetinal Ganglion Cells / metabolism
dc.subject.meshGlaucoma / drug therapy
dc.subject.meshGlaucoma / pathology
dc.subject.meshGlaucoma / metabolism
dc.subject.meshProdrugs / pharmacology
dc.subject.meshEstradiol / pharmacology
dc.subject.meshDisease Models, Animal
dc.titleThe Prodrug DHED Delivers 17beta-Estradiol into the Retina for Protection of Retinal Ganglion Cells and Preservation of Visual Function in an Animal Model of Glaucoma
dc.typeArticle
dc.type.materialtext

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