# Post-translational histone modification in ocular tissues of mice exposed to arsenicals

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $124,520

## Abstract

In this administrative supplement, we propose to expand animal models of ocular diseases and include a model
of ocular tissue damage caused by exposure to vesicant chemicals. In particular, we will focus on post-
translational histone modifications resulted from exposure to the blister agent Lewisite that is one of the most
powerful arsenic-based chemical warfare agents, exposure to which damages the human body by both systemic
tissue injury (e.g., to the lungs) and local injury (e.g., to the surface of the eye). LEW easily penetrates clothing
and personal protective equipment (PPE), making the exposed human population particular susceptible causing
acute skin, kidney and lung injuries. Therefore, we hypothesize that mice exposed to LEW either through
subcutaneous absorption, inhalation, or direct eye contact experience ocular tissue damage through the
mechanism of bromodomain 4 (BRD4)-mediated histone hyperacetylation and pro-inflammatory response, and
the development of arsenical prototypes accurately mimicking the LEW-induced molecular pathogenesis of the
eye will significantly facilitate the development of new counteractive measures. In aim #1, we propose to
investigate whether the cutaneous exposure of mice to Lewisite triggers ocular tissue damage and to identify the
molecular pathways involved in ocular tissue pathobiology. In aim#2, we will determine whether direct eye
exposure to Lew in mice causes ocular tissue damage through histone modification and altered gene
expression. In aim#3, we determine whether direct eye exposure to phenylarsine oxide (PAO) in mice causes
ocular tissue damage similar to LEW-induced ocular injury. We hypothesize that PAO, a relatively less toxic
Lewisite analog, mimics LEW-induced ocular pathogenesis and, therefore, whether it could be used to
validate newly designed antidotes targeting BRD4 to fight LEW-induced damage. We will focus on corneal
and retinal tissue damage through histology and molecular assessment. These data will establish for the first
time the cellular and molecular mechanisms responsible for arsenic-mediated ocular injury. The study will also
generate a therapeutic platform and overcome current technical difficulties in testing chemical warfare agents
for eye research in a laboratory setting to validate newly designed counteract measures. My research
expertise lies in the area of retinal degeneration which complements the proposed investigation in this project.

## Key facts

- **NIH application ID:** 10175917
- **Project number:** 3R01EY027763-03S1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Marina Gorbatyuk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $124,520
- **Award type:** 3
- **Project period:** 2020-09-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10175917

## Citation

> US National Institutes of Health, RePORTER application 10175917, Post-translational histone modification in ocular tissues of mice exposed to arsenicals (3R01EY027763-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10175917. Licensed CC0.

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