# Assessing how ocular surface nerves, immune cells, and epithelial cells communicate to encourage neuro-immune homeostasis

> **NIH NIH U01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $1,678,469

## Abstract

PROJECT SUMMARY
The nature and function of ocular surface nerves play a critical role in maintaining ocular surface health while
preventing disease. Disruption of ocular surface sensory nerves can lead to blinding keratitis, graft rejection,
dry eye disease, and ocular surface pain. The advent of “-omics” studies have provided a platform to
understand how ocular surface nerves participate in the broader context of ocular health and disease. Here,
we outline a proposal that will create large datasets detailing the nature of ocular surface innervation. We will
take a systems-level approach towards analyzing our data using bioinformatics and machine learning
platforms, so that we can gain a practical understanding of the ocular surface environment during health and
disease. Specifically, this proposal will address how ocular surface nerves, epithelial cells, and immune cells
interact. We have recruited a multidisciplinary research team that consists experts in ophthalmology,
neuroimmunology, neurology, proteomics, systems immunology, and bioinformatics. With this team, we plan to
comprehensively analyze all three levels of research outlined in the RFA, which includes anatomical and
morphological characterization, defining cellular and molecular properties of neuronal and non-neuronal cell
types, and assessing functional properties of neuronal and non-neuronal cells. Because innervation patterns
and functionality changes with disease, we will use multiple ocular surface disease models (viral keratitis and
aqueous dry eye disease) to better understand how neurons, epithelial cells, and immune cells affect neuronal
functionality and subsequent disease. We will achieve our goal by pursuing four specific aims: 1) We will
perform single-cell (sc)-omics on neuonrs and non-neuronal cells of the cornea and ocular surface innervating
ganglia. These data will characterize neuronal identities and describe their functionality during disease.
Additionally, we will be able to molecularly characterize immune and epithelial cells that influence the
functionality of ocular surface afferents during disease. 2) We will use mass spectrometry to analyze the
proteomic signatures of the cornea during health and disease. An unbiased shotgun approaches and a
targeted approach focusing on neurotrophic factors will be used to identify proteins that influence ocular
surface nerve functionality. 3) We will use our imaging techniques and histocytometry to comprehensively
analyze the location and morphology of neuronal and non-neuronal cells within the cornea, so that we may be
able to make conclusions about how nerves, epithelial, and immune cells interact in close proximity at the
ocular surface. 4) We will use DREADD (designer receptor exclusively activated by designer drugs) technology
to perturb neuronal sensitivity, so that we can assess how altering neuronal responsiveness to stimuli may
affect the ocular surface homeostasis and progress of disease. A systems-level analysis...

## Key facts

- **NIH application ID:** 10595234
- **Project number:** 1U01EY034711-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Daniel H Kaplan
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,678,469
- **Award type:** 1
- **Project period:** 2022-09-30 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10595234

## Citation

> US National Institutes of Health, RePORTER application 10595234, Assessing how ocular surface nerves, immune cells, and epithelial cells communicate to encourage neuro-immune homeostasis (1U01EY034711-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10595234. Licensed CC0.

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