# Blink, Lacrimation, and Nociception: Precision Mapping and Integrated Atlas Generation of Corneal Trigeminal Afferents

> **NIH NIH U01** · DUKE UNIVERSITY · 2024 · $1,300,835

## Abstract

ABSTRACT
Corneal nerves that mediate pain, blink reflexes and tear production are indispensable in the proper
maintenance of ocular surface homeostasis. However, the complexity of these neurons, both at the axon level
in the cornea, and cell bodies in the trigeminal ganglion, has made it increasingly difficult to grasp their full
nature, resulting in key knowledge gaps in the field. Consistent with the call for the current U01, we will
address this barrier via comprehensive analyses of corneal nerves at the morphologic, molecular, and
functional level. We have assembled a multidisciplinary team with complementary expertise, enabling
integrated analyses of spatial, electrophysiologic, genomic and behavioral profiles in mice; and AI-assisted
structure-function studies in human subjects, to open new inroads in the field. In Aim 1, we will anatomically
and functionally map corneal-projecting trigeminal afferents in mice. Genetic approaches will be applied to
rigorously profile the spatial arrangement of nociceptors in the cornea and trigeminal ganglion using seven-
color immunolabeling. This spatial information will be directly linked with the electrophysiological profiling of
these respective populations. In Aim 2, genomic analyses of corneal-projecting trigeminal afferents will be
conducted applying a new platform for spatial RNA-seq at cellular resolution. We will use mouse strains to
parse out the transcriptomes and behavioral outputs at the genetic level. Moreover, we apply two novel
approaches to selectively target corneal nerves involved in tear production versus blinking. In Aim 3, we will
discover morphological patterns of corneal nerves that predict blinking, lacrimation, and nociception in humans.
We will image corneal nerves with in vivo confocal microscopy of subjects with differential blink, tear, and
nociceptive behavioral outputs, thereby capturing functional analogs of the mouse experiments in Aims 1 and
2. With the AI-based auto-segmentation algorithm that we are developing, we will be able to apply machine
learning for multidimensional profiling of nerve patterns, and then compare these with respective behavioral
outputs. These AI-guided efforts will provide critical clues for understanding corneal afferent structure-function
in humans. In summary, our collective studies will lead to an unprecedented cartography of corneal afferents in
blink, lacrimation, and nociception. The advancements from this work will be poised to facilitate a deeper
understanding of related pathobiology including neuropathic ocular pain and dry eye disease that will lay the
foundation for future translational and clinical research. All genomic, imaging and electrophysiologic datasets
produced will be made publicly available, and all software products for corneal nerve image segmentation will
be made freely available online as open-source and easy-to-use software packages.

## Key facts

- **NIH application ID:** 10914969
- **Project number:** 5U01EY034687-03
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Sina Farsiu
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,300,835
- **Award type:** 5
- **Project period:** 2022-09-30 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914969

## Citation

> US National Institutes of Health, RePORTER application 10914969, Blink, Lacrimation, and Nociception: Precision Mapping and Integrated Atlas Generation of Corneal Trigeminal Afferents (5U01EY034687-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10914969. Licensed CC0.

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