# A Novel Neuroprotective Approach for Glaucoma

> **NIH NIH R01** · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · 2024 · $432,467

## Abstract

ABSTRACT
The broad goal of our continued research is to decipher the effect of estrogen deprivation, with or without
elevated intraocular pressure (IOP), on the vulnerability of the retina to neurodegeneration and to find a
preventative and/or curative pharmacological intervention to preserve the quality of vison under these
conditions. In the current grant period, we have shown that our prodrug approach (DHED) has produced the
powerful neuroprotectant, 17β-estradiol (E2), exclusively in the retina upon topical administration without
exposing the rest of the body to the unwanted side effects of the hormone. This distinguishing feature of DHED
has been demonstrated in both male and female animals. In an animal model of human glaucoma, we have
found that E2 produced locally from DHED protects the retinal ganglion cells (RGCs) from apoptosis, as well as
prevents visual impairment and functional deficits associated with the disease. Using proteomics, we have also
found that DHED eye drops successfully engaged E2-responsive therapeutic targets in the rat retinal proteome.
Through these studies, we have recognized that young, gonadectomized male and female animals with
normotensive IOP exhibit a proteomic landscape that is very similar to that of aged animals when compared to
young intact animals. Elevated IOP further disrupted vital protein expressions associated with signaling
networks involving neuroprotective targets and regulations of metabolic activities essential for retina health.
However, DHED eye drops completely alleviated the detrimental consequences of estrogen deprivation and
elevated IOP, suggesting that an “estrogenic” retina is needed for proper visual function. This application for
renewal addresses critical questions that stem from these collective findings. Specifically, is an E2-deprived
retina, regardless of age or elevated IOP, vulnerable to neurodegeneration, and can topical DHED be used as a
preventative and therapeutic agent to preserve the quality of vison under hypoestrogenic and/or elevated IOP
condition? Specific Aim 1 is designed to determine parameters of RGC neuroprotection and for the attenuation
of visual impairment afforded by DHED eye drops in E2-deprived animals compared to normotensive and
hypertensive ocular conditions. Proteomics- and phosphoproteomics-based studies in Specific Aim 2 will
investigate the mechanistic benefits of DHED eye drops in E2-deprived animals that exhibit normal versus
elevated IOP. Specific Aim 3 will utilize retina metabolomics to address metabolic dysregulations under
hypoestrogenic conditions and elevated IOP, compared to the amelioration of these alterations by topical DHED.
Through the integration of functional vision analyses with a multi-omics approach, we seek to advance our
understanding of E2 deprivation- and IOP-triggered ocular neurodegeneration, as well as its prevention or
treatment by topical DHED, in a comprehensive fashion.

## Key facts

- **NIH application ID:** 10772062
- **Project number:** 5R01EY027005-07
- **Recipient organization:** UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
- **Principal Investigator:** KATALIN T PROKAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $432,467
- **Award type:** 5
- **Project period:** 2016-08-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10772062

## Citation

> US National Institutes of Health, RePORTER application 10772062, A Novel Neuroprotective Approach for Glaucoma (5R01EY027005-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10772062. Licensed CC0.

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