# A novel hypotonic gelling eye drop for topical treatment of retinal degenerative diseases

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $409,375

## Abstract

PROJECT SUMMARY
Retinitis pigmentosa (RP) is a group of genetic diseases in which one of multiple different mutations in one of
more than 50 genes causes rod photoreceptor cell death. After most of the rods are eliminated, progressive
death of cone photoreceptors occurs, resulting in gradual loss of visual field that can result in blindness. There
are currently very few therapeutic options for RP, and the mechanism of cone cell death has been the subject
of intense study. We and others have identified oxidative and nitrosative damage as key in the progressive loss
of cone photoreceptors. We demonstrated that metipranolol, a nonselective β-adrenergic receptor antagonist
given orally for the treatment of arterial hypertension and topically for lowering intraocular pressure (IOP), also
reduces nitrosative stress and promotes cone survival and function in the rd10 mouse model of RP.
Importantly, topical administration 3x/day was more effective in preserving retinal function than daily
subcutaneous injections. However, it is much easier to deliver drugs to the retina with conventional eye drops
in mice than in larger eyes, and further, patients often do not adhere to dosing regimens requiring multiple
doses each day. To this end, we have discovered an approach for effectively delivering drugs to the retina in
large animals, including rabbits and pigs, with once daily topical eye drops. Our unique eye drop-based drug
delivery technology provides improved intraocular delivery of both water soluble and water insoluble drugs,
such as metipranolol. We hypothesize that a new hypotonic gelling eye drop formulation designed to maximize
the residence time, intraocular penetration, and drug delivery to the retina with minimal toxicity will be an
important step toward the development of a new once daily treatment for RP and other retinal degenerative
disorders. With metipranolol’s established ocular safety and tolerability in humans, it is an ideal candidate for
developing a first-of-its-kind eye drop for preserving vision in RP. In Specific Aim 1, we will develop and fully
characterize new polymer blends for optimal viscosity, shear thinning, spreading, gelation rate, and intraocular
penetration of metipranolol. In Specific Aim 2, we will test gelling formulations optimized for various key
properties versus standard liquid eye drops in mouse and rat models of RP. In Specific Aim 3, we will evaluate
ocular pharmacokinetics in pigs, which are considered the most relevant animal model to humans for topical
eye drop dosing, as the eye size and structure is the most similar, and thus most relevant for characterizing
delivery to the retina with a topical formulations. We will further evaluate ocular biocompatibility in rabbits, the
most commonly used animal model to assess safety of ocular products due to the similarities in eye structure
and the sensitivity of the eye to potential toxicity. If these preclinical studies progress as expected, we will be
well-positione...

## Key facts

- **NIH application ID:** 9865104
- **Project number:** 1R01EY031041-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Peter A Campochiaro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,375
- **Award type:** 1
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9865104

## Citation

> US National Institutes of Health, RePORTER application 9865104, A novel hypotonic gelling eye drop for topical treatment of retinal degenerative diseases (1R01EY031041-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9865104. Licensed CC0.

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