# Understanding neural control of the ocular surface

> **NIH NIH U01** · CASE WESTERN RESERVE UNIVERSITY · 2024 · $1,444,600

## Abstract

Project Summary
 Currently our understanding of how the nervous system maintains ocular surface homeostasis is extremely
limited. New technologies, methods and models are needed to advance our scientific understanding and address
knowledge gaps. The ocular surface and tear film-secreting glands (including the lacrimal and meibomian glands,
as well as the goblet cells) are carefully controlled to provide an optically smooth, low-scattering surface with
appropriate immune and injury responses. Sensory feedback to maintain the structural and functional integrity
of the ocular surface is provided by the corneal nerves, which send feedback from stimuli (chemical, thermal,
mechanical) to ganglia (e.g., trigeminal) and brain regions (e.g., ventral posteromedial thalamus) to drive
production of tear film components as well as the blink reflex. This delicate balance of neural control is disrupted
by damage, peripheral neuropathies, inflammation and further complicated by a wide array of immune responses
to various diseases. Dysfunction of this feedback loop can lead to a downward spiral of further dysregulation.
Aberrant neural control of the ocular surface can lead to abnormal sensation and pain, which in the worst cases
can be disabling. To find remedies, it is first essential to understand the underlying neural control system and
how it adapts to its environment.
 In this proposal, we aim to bring new tools and models to study molecular, cellular, and functional interactions
across systems responsible for neural control of the ocular surface and examine how they change under different
inflammatory and pain conditions. We have assembled an excellent team with expertise across multiple fields
including advanced 3D microscopy, neuroscience, electrophysiology, pain, ocular immunology, ocular lipid
metabolism, ocular surface disorders, spatial statistics, and machine/deep learning. Here, we will utilize cutting
edge techniques and technologies including optical clearing, tract tracing, ethologically-valid behavior analysis,
machine/deep learning, spatial statistics, genetically encoded calcium imaging, light-sheet microscopy,
multiplexed 3D fluorescence in situ hybridization (FISH) imaging, and multi-array electrodes implanted in the
brain. These tools will help us assess molecular, cellular, and functional interactions across organs and begin to
understand ocular surface control at the organism level. We will also employ several relevant animal models to
assess ocular surface control under different inflammatory and pain conditions. Models include AWAT2 deficient
mice that mimic evaporative dry eye disease (DED), diabetic mice, an epithelial debridement model with
Pseudomonas aeruginosa that mimics bacterial keratitis, and human donor eyes. The mouse models all have
gCaMP6f expressed in corneal nerves allowing functional imaging of calcium transients. With these models we
will study both innate and adaptive immunity as well as nociceptive and neuropathic p...

## Key facts

- **NIH application ID:** 10915035
- **Project number:** 5U01EY034693-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** MICHAEL W. JENKINS
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,444,600
- **Award type:** 5
- **Project period:** 2022-09-30 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10915035

## Citation

> US National Institutes of Health, RePORTER application 10915035, Understanding neural control of the ocular surface (5U01EY034693-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10915035. Licensed CC0.

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