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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

Authors :
Ammar Kapic
Khadiza Zaman
Vien Nguyen
George C. Neagu
Nathalie Sumien
Laszlo Prokai
Katalin Prokai-Tatrai
Source :
Cells, Vol 13, Iss 13, p 1126 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

We report a three-pronged phenotypic evaluation of the bioprecursor prodrug 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED) that selectively produces 17β-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.

Details

Language :
English
ISSN :
20734409
Volume :
13
Issue :
13
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.96fc23a8b1348c79b345433a2125916
Document Type :
article
Full Text :
https://doi.org/10.3390/cells13131126