Abstract
We examined the impact of 17β-estradiol (E2) eye drops on the modulation of the proteome profile in the male rat retina. With discovery-driven proteomics, we have identified proteins that were regulated by our treatment. These proteins were assembled to several bioinformatics-based networks implicating E2’s beneficial effects on the male rat retina in a broad context of ocular neuroprotection including the maintenance of retinal homeostasis, facilitation of efficient disposal of damaged proteins, and mitochondrial respiratory chain biogenesis. We have also shown for the first time that the hormone’s beneficial effects on the male retina can be constrained to this target site by treatment with the bioprecursor prodrug, DHED. A large concentration of E2 was produced after DHED eye drops not only in male rat retinae but also in those of rabbits. However, DHED treatment did not increase circulating E2 levels, thereby ensuring therapeutic safety in males. Targeted proteomics focusing on selected biomarkers of E2’s target engagement further confirmed the prodrug’s metabolism to E2 in the male retina and indicated that the retinal impact of DHED treatment was identical to that of the direct E2 treatment. Altogether, our study shows the potential of topical DHED therapy for an efficacious and safe protection of the male retina without the unwanted hormonal side-effects associated with current estrogen therapies.
Highlights
Accumulating evidence shows that 17β-estradiol (E2) impacts the retina and, in general, the central nervous system (CNS) through well-orchestrated genomic and nongenomic actions that tackle numerous pathways implicated in CNS-related pathological processes [1,2]
In a follow-up study, we have shown the positive impact of E2 eye drops on the protein networks in the context of biological processes in the female rat retina through quantitative proteomics [13]
Relying on our discovery-driven proteomics approach [13], we have identified several protein networks influenced by E2 in the male rat retina
Summary
Accumulating evidence shows that 17β-estradiol (E2) impacts the retina and, in general, the central nervous system (CNS) through well-orchestrated genomic and nongenomic actions that tackle numerous pathways implicated in CNS-related pathological processes [1,2]. These processes include the initiation and propagation of neurodegeneration currently without viable therapeutic options [3,4,5]. One of the most common ocular neurodegenerations is seen in glaucoma [6] In this group of diseases, gradual and irreversible damage to the retinal ganglion cells (RGCs) and their axons lead to visual disability or even blindness in spite of controlling the intraocular pressure (IOP) [7,8].
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