# The role of galectin-8 in the regulation of corneal infection and inflammation

> **NIH NIH R01** · TUFTS UNIVERSITY BOSTON · 2020 · $412,500

## Abstract

Project Summary
The bacterium Pseudomonas aeruginosa (PA) is a leading cause of microbial infection of the cornea. One of the
serious consequences of PA corneal infection is blindness resulting from persistent corneal inflammation.
Approximately 30,000 cases of microbial keratitis occur annually in the United States. The innate immune system
is the first line of defense against pathogens and is initiated by pattern recognition receptors which respond to
invading microbes. It is known that IL-1β plays an important role in the induction of immune response in PA
keratitis. In the classical immune response to bacterial infection, generation of mature IL-1β is a two-step
process. The first step is the induction of pro-IL-1β expression, which is generally achieved by TLR-mediated
activation of NF-B pathway that results in the induction of pro-IL-1β. A second signal then triggers the assembly
of inflammasomes leading to the cleavage of caspase-1. Active (cleaved) caspase-1 cleaves pro-IL-1β to
generate active IL-1β, which is secreted from the cell to mediate downstream inflammatory effects that clear the
infection. Recently, we have made an exciting observation that galectin-8 knockout (Gal-8 KO) mice are resistant
to PA infection. Additional pilot studies revealed that Gal-8 has the potential to regulate the activation of both
TLR and inflammasome pathways. The goal of this project is to characterize the role of Gal-8 in the regulation
of PA-induced immunopathology, and to develop effective strategies for prevention and regression of
uncontrolled inflammatory response that results in extensive damage to the cornea and visual impairment. In
Aim 1, in an effort to understand the mechanisms that render Gal-8 KO mice resistant to PA keratitis, we will test
the hypothesis that Gal-8 has the capacity to dampen inflammasome-mediated generation of mature IL-1β to
influence innate immune response. Specifically, in this Aim, using Gal-8 KO mice and Gal-8 deficient
macrophages and neutrophils, we will characterize the role of Gal-8 in the regulation of the inflammasome
pathway in PA keratitis. In Aim 2, we will determine whether Gal-8 influences the outcome of PA keratitis by
modulating neutrophil elastase and/or TLR pathway. To better characterize the role of Gal-8 in the pathogenesis
of PA keratitis, in Aim 3A, we propose to perform transcriptome and cytokine/chemokine proteome analyses of
PA-infected corneas of WT and Gal-8 KO mice, and WT and Gal-8 KO macrophages and neutrophils. In Aim
3B, studies will be performed to determine whether Gal-8 can be targeted to control overactive immune response
and corneal inflammation in the mouse model of PA keratitis. We expect that the proposed study will provide
ground-breaking data, not only for understanding the molecular mechanism of PA keratitis, but also for the
development of novel, galectin-based therapy that can treat blinding immunopathology resulting both from
bacterial keratitis, as well as from other ocular...

## Key facts

- **NIH application ID:** 9933036
- **Project number:** 5R01EY028570-03
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Noorjahan Panjwani
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2018-09-30 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933036

## Citation

> US National Institutes of Health, RePORTER application 9933036, The role of galectin-8 in the regulation of corneal infection and inflammation (5R01EY028570-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9933036. Licensed CC0.

---

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