# Postnatal Mice as a Pediatric Research Model for Investigating Direct Ocular Exposure to Vesicants

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $146,855

## Abstract

Our proposal builds upon preliminary data from robust published studies conducted by our research group
involving adult mice exposed to powerful vesicants, such as lewisite (LEW) and nitrogen mustard (NM). We
were among the first to recognize the detrimental effects of these agents on retinal health, which prompted us
to investigate the molecular mechanisms underlying ocular and retinal tissue deterioration upon direct ocular
exposure (DOE) to vesicants. While several research groups, including ours, are actively investigating potential
molecular drivers of ocular tissue damage in adults, there is currently a lack of understanding of how vesicant
exposure impacts the most vulnerable segments of our society, such as infants, juveniles, pregnant females,
and the elderly. In this proposal, we aim to test the hypothesis that children are more susceptible to the same
dose of DOE than adults due to the small size of the former’s eye globes and the differences in metabolic rates
of ocular tissues. We will explore the mechanisms behind this increased vulnerability in children and propose a
comparative study between DOEs in postnatal and adult mice. Two vesicants are proposed for this study. First,
we plan to determine whether postnatal day (p) 20 C57BL6 mouse pups are more susceptible than adult mice
to DOE to phenylarsine oxide (PAO), a known and validated surrogate of LEW. Second, we intend to research
whether p20 C57BL6 mouse pups are more susceptible to DOE to NM than adult mice. Finally, we will
investigate the key molecular signaling that is reprogramed upon postnatal DOE to PAO and NM compared to
adult DOE. These data will provide evidence that DOE to vesicants is toxic for children and will identify them as
the most vulnerable segment of exposed populations. This research will also validate p20 pups as a pediatric
eye research model to study DOE to vesicants and establish, for the first time, the cellular and molecular
mechanisms responsible for vesicant-mediated ocular injury. Additionally, this study will generate a therapeutic
platform to overcome current technical difficulties in testing chemical warfare agents (CWA) for pediatric
ophthalmic research and validate newly designed medical countermeasures (MCM).

## Key facts

- **NIH application ID:** 11083239
- **Project number:** 3R01EY034110-02S1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Marina Gorbatyuk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $146,855
- **Award type:** 3
- **Project period:** 2022-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11083239

## Citation

> US National Institutes of Health, RePORTER application 11083239, Postnatal Mice as a Pediatric Research Model for Investigating Direct Ocular Exposure to Vesicants (3R01EY034110-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11083239. Licensed CC0.

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