# The Role of Master Epigenetic Regulators in Ocular Chemical Injury

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2024 · $480,000

## Abstract

The Role of Master Epigenetic Regulators in Ocular Chemical Injury
SUMMARY
Mustard vesicants including sulfur mustard (SM) and nitrogen mustard (NM) cause severe respiratory, skin,
and ocular injuries. They have been used as a chemical weapon in the warfare and also impose a potential
threat to civilians as they could be used by the terrorists' attack. Ocular injuries in particular corneal injury were
prevalent in SM-exposed victims. Inflammation, neovascularization and fibrosis are three major problems and
players in mustard-induced corneal injury, yet the underlying mechanisms are largely unknown, which limits
the development of effective managements for the disease. The BET (bromodomain and extra-terminal
domain) family proteins, including universally expressed BRD2, BRD3 and BRD4 and testis-specific BRDt, are
epigenetic readers. They recognize and bind to acetylated lysine (KAc) within the N-terminal tail protruding
from the histone core of the nucleosome, and act as scaffold proteins to recruit transcription factors and the
positive transcription elongation factor b (P-TEFb) complex, which phosphorylates and releases paused RNA
polymerase II (RNAPII) to transcript the transcription factor-targeted genes. The BETs play a key role in
inflammation, neovascularization and fibrosis in many disease but their role in ocular chemical injury is
unknown. We now provide compelling evidence suggesting that BETs have a key role in corneal mustard injury
and propose to further explore this novel mechanism. We will test the hypothesis that NM injury induces
corneal inflammation, neovascularization and fibrosis via activation of master epigenetic regulator BETs using
mouse and rabbit models, selective BTE inhibitors, state of the art in vivo ocular imaging techniques including
optical coherence tomography (AS-OCT) and OCT-angiography (OCT-A), and genomic profiling and
immunohistochemistry approaches. The proposed work will allow us to define the role of BETs in mustard-
induced injury by characterizing the contributions of BD1 and BD2 in corneal injury, elucidating the underlying
mechanisms, and testing whether BET inhibition could effectively treat acute and delayed injury. Considering
the success that has been reported in developing BET blockers with acceptable safety profiles and promising
efficacy in several phase I and II clinical trials, BET inhibitors may offer high translational potentials for being
tested and eventually used in clinical studies.

## Key facts

- **NIH application ID:** 10896346
- **Project number:** 5R01EY034266-03
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Massoud Motamedi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $480,000
- **Award type:** 5
- **Project period:** 2022-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896346

## Citation

> US National Institutes of Health, RePORTER application 10896346, The Role of Master Epigenetic Regulators in Ocular Chemical Injury (5R01EY034266-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10896346. Licensed CC0.

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