# The miR-183/96/182 Cluster in Pseudomonas aeruginosa-induced Keratitis

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2024 · $433,641

## Abstract

Pseudomonas aeruginosa (PA) keratitis is one of the most rapidly developing and destructive diseases of the
cornea and a global cause of visual impairment and blindness. Emergence of antibiotic-resistant strains poses
additional challenges for effective disease management. Development of alternative treatment is urgent.
In this regard, microRNAs (miRNAs) are small, non-coding RNAs and important regulators of gene expression.
miRNAs play critical roles in human diseases and are viable therapeutic targets. However, the roles of miRNAs
in PA keratitis remain largely unexplored. Our long-term objectives are to uncover the molecular mechanisms
of miRNAs in ocular infectious diseases, identify novel miRNA-based therapeutic targets and develop
alternative treatment of these diseases. The proposed research will directly address this knowledge gap. It is
built upon our recently published and strong preliminary data showing that application of anti-miRs targeting
the miR-183/96/182 cluster (referred to as miR-183C from here on) and knockout of miR-183C in mice
decreases corneal nerve density and neuropeptide production, while reducing the severity of PA keratitis; miR-
183C targets key genes regulating corneal sensory innervation, e.g., Nrp1, bacterium-induced sensory-neuron
activation and neuropeptide production, e.g., Toll-Like Receptor (TLR)4, Formyl Protein Receptor (Fpr)1 and
substance P (sP) precursor gene Tac1. These data lead us to the overarching hypothesis that, in addition to
innate immunity, miR-183C modulates PA keratitis through its regulation of corneal sensory nerve function and
neuroimmune interaction by targeting key genes involved in sensory innervation, PA-induced sensory-neuron
activation and pro-inflammatory neuropeptide production. Three Aims are proposed in this application to test
this hypothesis. In Aim 1, fluorescein amidites (FAM)-labeled anti-miR-183C will be applied to the cornea of
wild-type (WT) mice to test the hypothesis that anti-miR-183C treatment upregulates Tac1, TLR4, Fpr1 and
Nrp1 in corneal sensory nerves, resulting in increased pro-inflammatory neuropeptides (e.g., sP) and an early
immune/inflammatory response (<24 hours post-infection) and an accelerated sensory-nerve reduction and
decreased pro-inflammatory neuropeptides and immune/inflammatory response in a later stage during disease
resolution. Aim 2 will test the hypothesis using a sensory neuron-specific miR-183C conditional knockout
mouse model. Aim 3 will test the hypothesis that knockdown or knockout of miR-183C in vitro/ex vivo in both
human and mouse sensory neurons parallels the in vivo data in that it will upregulate Tac1, TLR4 and Fpr1 to
enhance PA-induced secretion of pro-inflammatory neuropeptides by sensory neurons, and increase Nrp1
expression to inhibit neurite growth. A genome-wide identification of miR-183C target genes in both human and
mouse trigeminal ganglion sensory neurons will also be conducted by RNA seq.
This study will provide novel ...

## Key facts

- **NIH application ID:** 10874775
- **Project number:** 5R01EY026059-07
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** SHUNBIN XU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $433,641
- **Award type:** 5
- **Project period:** 2017-04-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874775

## Citation

> US National Institutes of Health, RePORTER application 10874775, The miR-183/96/182 Cluster in Pseudomonas aeruginosa-induced Keratitis (5R01EY026059-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10874775. Licensed CC0.

---

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