# Tools to study corneal nerve signaling

> **NIH NIH R21** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $191,517

## Abstract

Project Summary
The cornea is the most densely innervated structure within the human body. Aberrant corneal nerve function is
associated with diseases such as diabetes and direct eye issues such as neurotrophic keratopathy, corneal
opacities, dry eye syndrome, and keratoconus. Some neurological disorders (e.g., migraines) are correlated
with abnormal corneal nerve patterning which is likely to profoundly influence corneal signaling. Understanding
how corneal nerve signaling changes during normal development and during disease progression, such as
type 2 diabetes, may provide insight into the etiology of eye diseases and neurological disorders in general.
Also, corneal nerve damage or dysfunction can originate following a variety of surgeries, including laser in situ
keratomileusis (LASIK), small incision lenticule extraction (SMILE), laser epithelial keratomileusis (LASEK),
and photorefractive keratectomy (PRK). Knowledge of corneal nerve signaling is very limited at present. Before
progress on understanding the role of corneal nerve function in disease states can be made, better tools need
to be developed and refined.
 Recent studies have utilized genetically encoded Ca2+ indicators (GECIs) to allow high-fidelity Ca2+
imaging in excitable cells to help understand neural circuitry. When paired with the appropriate promoter,
murine models express GECIs in specific neural subtypes or in all neurons. Our group has recently designed a
GECI mouse that expresses a Ca2+ indicator (GCaMP6f) in corneal nerves which could lead to development of
an imaging platform to overcome previous limitations (e.g., requires contact, inability to measure from
individual cells or axons, small field of view) in recording corneal nerve signaling. Our group also has extensive
experience applying infrared neuromodulation to a wide variety of tissues. In order to decode neural circuits, it
is important to both measure and perturb signals from an entire network.
 The goal of this proposal is to establish the feasibility of using genetic indicators for assessing corneal
nerve function. Although GECIs have never been used for imaging in the cornea, it is a particularly appealing
target. Since the cornea is transparent, has low auto-fluorescence, and nerves are sparse in the axial direction,
it is likely that very high signal to noise can be achieved and large fields of view can be interrogated. In this
project, we will build a high-speed fluorescence microscope system capable of infrared neuromodulation,
develop animal handling protocols (e.g., animal restraint with stereotactic system), and perform a pilot study
(effect of stimuli on diabetic and control mice). If successful this approach can fill the extensive gap in
technology and finally provide an exciting new platform for uncovering critical questions on how corneal nerves
function under normal conditions, during the etiology of disease, and during the application of potential new
drugs and therapies.

## Key facts

- **NIH application ID:** 10126017
- **Project number:** 5R21EY031525-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** MICHAEL W. JENKINS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $191,517
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126017

## Citation

> US National Institutes of Health, RePORTER application 10126017, Tools to study corneal nerve signaling (5R21EY031525-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10126017. Licensed CC0.

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