# Interleukin-1a in fungal keratitis

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $22,752

## Abstract

PROJECT SUMMARY/ABSTRACT:
 Fungal keratitis is an infection of the corneas by pathogenic fungal species that is notoriously resistant
to treatment and could lead to permanent blindness. Conidia (fungal spores) are ubiquitous in the environment
and can infect healthy individuals following ocular trauma or unsanitary contact lens use. Once in the corneal
stroma, conidia germinate resulting in rapid hyphae formation and tissue infiltration. Neutrophils are the first
cells recruited to the corneas, and play a critical role in the host response against infection. While they are
necessary to eliminate fungi, neutrophils also contribute to severe tissue damage. Current treatment includes
antifungal agents followed by corticosteroids to suppress the inflammatory response. However, if the pathogen
persists, this could lead to rapid hyphae invasion in the absence of an immune response. Therefore, there is a
need for a more targeted treatment for inflammation to better control the balance between fungal clearance
and tissue damage. To address this issue, we used Nanostring gene array analysis to analyze inflammatory
genes that might be up- or down-regulated in neutrophils responding to fungal keratitis. We found that sorted
neutrophils from the corneas of Aspergillus-infected mice highly upregulated Interleukin-1α (IL-1α) by >10,000
fold compared to bone marrow neutrophils.
 IL-1α is a pro-inflammatory cytokine that is critical for various infections. It is released by corneal
epithelial cells as an alarmin to initiate and amplify inflammation, and can indirectly recruit neutrophils. IL-1α
secretion is independent of the ER/golgi transport system. Many aspects of its biogenesis, regulation, and
secretion are not well understood. Based on preliminary data, I hypothesize that IL-1α plays a critical role in
the immune response during fungal keratitis. In this proposal, I will address three aims to support my
hypothesis: 1) determine the importance of neutrophil-derived IL-1α during the inflammatory stages of
Aspergillus keratitis, 2) define the role of corneal epithelial cells-derived IL-1α during disease, and 3) dissect
the mechanism for IL-1α secretion from live neutrophils. The proposed research will address many unknown
aspects of IL-1α, corneal epithelial cells, and neutrophil biology in response to fungal keratitis to provide a
better understanding of the inflammatory processes involved.

## Key facts

- **NIH application ID:** 10405442
- **Project number:** 5F31EY032312-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Bridget Ratitong
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $22,752
- **Award type:** 5
- **Project period:** 2021-03-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405442

## Citation

> US National Institutes of Health, RePORTER application 10405442, Interleukin-1a in fungal keratitis (5F31EY032312-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10405442. Licensed CC0.

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