# Phage-Based Therapeutics for Ocular Infections

> **NIH NIH R21** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2021 · $210,975

## Abstract

PROJECT SUMMARY / ABSTRACT
 Ocular bacterial infections cause a significant number of cases of blindness worldwide. Efforts to
prevent damage to delicate ocular tissues during infection rely on swift and proper use of therapeutics to
rapidly kill organisms and arrest damaging inflammation. Mainstay antibiotics currently approved for ocular
use can kill ocular pathogens. However, given the speed at which these infections can evolve, the emergence
of multidrug resistant (MDR) ocular pathogens, the delicate nature of ocular tissue, and the importance of
proper visual acuity, halting these infections as soon as possible is critical to patients’ ocular health. Alternative
antimicrobial strategies which result in rapid killing of organisms in the eye would provide a significant
improvement over that of mainstay antibiotics which allow replication due to their slow activities, or antibiotics
that are ineffective due to MDR pathogens.
 Bacteriophage-based therapeutics have gained traction as a last line experimental strategy for the
treatment of patients infected with MDR pathogens. Efficacy testing of phages and, more recently, phage
lysins, in treating bacterial infections is not new. However, their use in treating ocular infections of all types in a
broad-spectrum regimen in eye infections has not been studied. Our goal is to create a phage lysin cocktail
which can be administered to the eye during infection, resulting in rapid killing of those organisms, mitigation
of inflammation, and preservation of vision. We hypothesize that because phage lysins rapidly lyse
bacteria prior to phage exit, these lysins will rapidly kill bacteria in ocular tissues during infection.
Preliminary data demonstrates feasibility and success in phage lysin-mediated killing of S. aureus in the eyes
of mice. The next steps are to test the efficacy of phage lysins in killing other ocular bacterial pathogens in
experimental models of keratitis and endophthalmitis (Aim 1), and then combine and test phage lysins of
different bacteria in a broad-spectrum cocktail in these models against MDR pathogens (Aim 2).
 A critical barrier to clinical improvements in ocular bacterial infections is the use of mainstay
antibiotics that may not kill efficiently enough. We have reported that regardless of the offending pathogen,
bacterial replication in the eye triggers acute inflammation in response to an increasing innate immune agonist
burden and results in toxin production which leads to tissue damage. These studies will determine whether
phage lysins kill ocular pathogens more efficiently than mainstay antibiotics, resulting in improvements in
therapeutic outcome. If effective, the next step is to test the phage lysin cocktails with innate pathway-based
anti-inflammatory agents, which we are also pursuing. Testing of phage lysins in the treatment of ocular
bacterial infections is novel, high-impact, translationally relevant, and will positively influence the
ocular infectious disease field...

## Key facts

- **NIH application ID:** 10219273
- **Project number:** 5R21EY031802-02
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Michelle C Callegan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $210,975
- **Award type:** 5
- **Project period:** 2020-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219273

## Citation

> US National Institutes of Health, RePORTER application 10219273, Phage-Based Therapeutics for Ocular Infections (5R21EY031802-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10219273. Licensed CC0.

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