# Functional significance of NETosis to intraocular inflammation

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2020 · $264,750

## Abstract

Abstract
 Uveitis can result in severe visual impairment, and ranks fifth among causes of blindness in the
United States. Yet we are still trying to develop a complete understanding of the mechanisms of non-
infectious intraocular inflammation. Expanding our knowledge of the role innate immunity plays in non-
infectious inflammatory disease will provide important insights to complement the large body of
literature on the role adaptive immunity, particularly T-cells, play in intraocular inflammation. Neutrophils
are important innate immunity effector cells, and have been identified in human eyes with uveitis as well
as in experimental models of uveitis. Neutrophils can undergo a form of cell death known as NETosis
as part of the host response to infection, or during sterile inflammation in autoimmune diseases. The
resulting neutrophil extracellular traps (NETs) can be pro-inflammatory, and blocking NETosis has been
shown to ameliorate inflammation in animal models of systemic inflammatory diseases. Despite the
presence of neutrophils in inflamed eyes, the presence of NETs in uveitis has not been explored.
 We have preliminary data identifying NETs in an animal model of anterior and intermediate
uveitis, primed mycobacterial uveitis (PMU). We propose using both PMU and experimental
autoimmune uveitis (EAU) to determine if NETs are generally present in the case of intraocular
inflammation (Aim 1). We will also determine the functional importance of NETs to uveitis by testing the
sufficiency of NETs to generate uveitis and the impact of blocking NETosis with genetic and chemical
inhibition (Aim 2). These studies will advance the field of innate immunity in ocular inflammation, and
provide pre-clinical evidence for NETosis as a therapeutic target for drug development of new
treatments for patients with uveitis.

## Key facts

- **NIH application ID:** 9906934
- **Project number:** 5R21EY029391-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Kathryn Pepple
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $264,750
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906934

## Citation

> US National Institutes of Health, RePORTER application 9906934, Functional significance of NETosis to intraocular inflammation (5R21EY029391-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9906934. Licensed CC0.

---

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