# Targeting Citrullination in Ocular Chemical Injury

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2022 · $246,000

## Abstract

Abstract:
The arsenal of chemical weapons developed for warfare continues to be a homeland security
threat, as these agents can be deployed to cause mass casualty. Vesicant agents, such as
sulfur mustard and nitrogen mustard cause severe acute injury in the affected ocular and lung
tissues with serious long-term consequences on vision due to fibrotic scarring. Thus, treatments
for such injuries are challenging, because they will have to be deployed in manner conducive for
rapid mass delivery under non-ideal conditions similar to battlefields. Exposure to sulfur mustard
also affects the internal retinal tissues in humans, and hence, consideration must be taken that
the whole eye is at risk. Serious eye injury to both the cornea and retina also occurs from
exposure to sodium hydroxide, a caustic agent that has been well studied. Thus, one could
repurpose the pathobiology of alkali injury and predict targets and pathways that would likely be
engaged in injuries produced by the mustards. Investigating alkali injury, we have unraveled that
this chemical causes potent increase in retinal gliosis and hypercitrullination acutely.
Citrullination is a posttranslational modification that is linked to a number of fibrotic diseases. We
showed that hypercitrullination is driven by expression of peptidyl arginine deiminase (PAD)-4.
Demonstrating that PAD4 is druggable in a post injury treatment paradigm, we showed PAD4
inhibition results in potent blockade of hypercitrullination. Thus, in this R21 grant proposal to the
NIH CounterACT program, we plan to examine the citrullination pathway in nitrogen mustard
injury employing mouse and rabbit corneal injury models. Our plan is to demonstrate that
hypercitrullination is an important pathological process in nitrogen mustard injury and test the
hypothesis that PAD4 is the principal driver of protein citrullination. Hence, we plan to use both a
small molecule inhibitor and PAD4-genetic deficiency paradigms to help validate this druggable
target. Our ultimate goal is to illuminate novel druggable targets and unravel a treatment
paradigm that will help develop future collaborations for drug development and aligned with the
CounterACT program.

## Key facts

- **NIH application ID:** 10459390
- **Project number:** 5R21EY032741-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** ROYCE MOHAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $246,000
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459390

## Citation

> US National Institutes of Health, RePORTER application 10459390, Targeting Citrullination in Ocular Chemical Injury (5R21EY032741-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10459390. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*