# Topical drug delivery formulations for neuroprotection in glaucoma

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $539,249

## Abstract

PROJECT SUMMARY
Glaucoma is a major cause of blindness, affecting over 80 million people worldwide. Glaucoma is a
neurodegenerative optic neuropathy caused by the loss of retinal ganglion cells (RGC), leading to loss of
vision. Current therapies are all directed at lowering intraocular pressure (IOP), and yet RGC loss still
continues in many patients despite IOP lowering. The identification of an agent that complements IOP lowering
by promoting RGC survival would be a significant advance toward improving the visual outcomes of patients
with glaucoma. Using cultures of primary RGC, we screened more than 10,000 compounds and identified
candidates with potent neuroprotective properties, including a drug that is FDA-approved for an unrelated
indication. We further characterized the novel pathway through which these compounds act to protect RGC,
thus identifying a novel drug/drug target combination for neuroprotection. We have also developed a novel
thermosensitive gel-forming eye drop drug delivery system that provides efficacious drug delivery to the
posterior segment, even in large animals (rabbits, pigs). Importantly, we observed that the combination of more
effective intraocular drug penetration provided by the gel-forming eye drop with a drug that binds to melanin in
the eye, led to RGC protection in vivo with once weekly topical dosing. In this application, we are screening
additional neuroprotective drugs for melanin binding, cell uptake, and intraocular penetration to compare head-
to-head for pharmacokinetics and efficacy in an optic nerve crush rat model and a bead injection mouse model
of IOP elevation. The goal is to develop an efficacious eye drop for neuroprotection that requires once weekly,
or ideally once monthly maintenance dosing. In Aim 1, we will make further formulation changes in the eye
drop to increase intraocular drug absorption, and formulate additional melanin-binding neuroprotective drugs.
In Aim 2, we will characterize the pharmacokinetics and efficacy of a variety of dosing regimens and
formulations to identify the most effective dosing approach with the lowest dosing frequency. In Aim 3, we will
perform dose-ranging studies in rabbits to achieve similar drug concentrations in target tissues that were
shown to be effective in Aim 2. We will also perform safety evaluations with longitudinal dosing, including
fundus exams, IOP, and retinal morphology analyses. The demonstration of efficacy in rodent models of
neurodegeneration along with similar pharmacokinetics and no overt toxicity in the rabbit eye, would provide
evidence of the therapeutic potential of our neuroprotective drug delivery strategy for the treatment of
glaucoma.

## Key facts

- **NIH application ID:** 10802881
- **Project number:** 1R01EY034902-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Laura Ensign
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $539,249
- **Award type:** 1
- **Project period:** 2024-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802881

## Citation

> US National Institutes of Health, RePORTER application 10802881, Topical drug delivery formulations for neuroprotection in glaucoma (1R01EY034902-01A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10802881. Licensed CC0.

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