# Underpinnings of corneal innervation: anatomical, molecular, and functional studies of corneal sensory afferents in physiologic and pathologic states

> **NIH NIH U01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $1,195,210

## Abstract

PROJECT ABSTRACT
A rich network of sensory afferents in the ocular surface (OS), supplied by the ophthalmic branch of the trigeminal
nerve, performs a multitude of physiological functions, including sensation, regulation of various reflexes, and
secretion of trophic and growth factors. Of the OS structures, the cornea is the most highly innervated tissue in
the body. As such, dysfunction of the corneal/OS nerves has been shown to underlie a wide range of diseases,
including trauma, infections, metabolic imbalances, and therapeutic interventions such as refractive surgeries.
Corneal diseases continue to be a major health problem in the US, and corneal nerve dysfunction contributes to
many of these disorders, such as neurotrophic keratitis, corneal neuropathic pain, and dry eye disease (DED).
DED alone has been shown to impact up to 75% of a given population, causing significant reduction in quality
of life and increased risk for visually debilitating opacities. Therefore, a comprehensive characterization of
corneal sensory nerves is critical for understanding the pathophysiology leading to OS diseases. To meet this
challenge and in response to the FOA RFA-EY-21-004 on OS innervation, we have assembled an
interdisciplinary team with a strong collaborative track record and complementary expertise, including eye
disease models and wound healing (Lee); pain and the mammalian somatosensory system (Luo); intravital
corneal nerve fiber imaging and regeneration (Rompolas); single-cell transcriptomics/epigenomics and
related computational analyses (Wu); and neurophysiology and data analysis/machine learning (Ding). We
propose to combine advanced imaging approaches, novel single-cell multi-omics, and cutting-edge mouse
genetic models to perform three levels of analysis: 1) Morphology - using single neuron genetic labeling, we will
resolve the fine morphology, spatial organization, and connectivity of corneal sensory neurons by visualizing
axonal arborization in the cornea and brainstem/spinal cord. We will also examine interactions of individual
sensory afferents and corneal epithelial cells. 2) Molecular - we will perform integrated single-cell transcriptomics
and epigenomics to interrogate the subtype-specific marker gene expression and epigenetic landscape of the
corneal sensory neurons. 3) Functional - we will perform real-time physiologic analyses of corneal sensory
afferents using in vivo two-photon calcium imaging. To further elucidate the role of sensory nerves in OS
pathophysiology, we will determine how their morphology, molecular profile, and responsiveness are altered in
a surgically induced DED model. Moreover, we will implement a novel high-speed imaging and machine learning
platform to quantify evoked responses to corneal sensory stimuli and spontaneous behavior in the DED model.
Taken together, our study will generate a comprehensive data set poised for integration that will fill in critical
knowledge gaps in the field, create a robust found...

## Key facts

- **NIH application ID:** 10584446
- **Project number:** 1U01EY034681-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Vivian Lee
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,195,210
- **Award type:** 1
- **Project period:** 2022-09-30 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10584446

## Citation

> US National Institutes of Health, RePORTER application 10584446, Underpinnings of corneal innervation: anatomical, molecular, and functional studies of corneal sensory afferents in physiologic and pathologic states (1U01EY034681-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10584446. Licensed CC0.

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