# The Neural Basis of Ocular Sensations

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $470,405

## Abstract

ABSTRACT
 Dry eyes and contact lens wear often cause foreign body sensation. This abnormal mechanosensation
is associated with “Lid Wiper Epitheliopathy” (LWE), a condition induced by the mechanical damage to the
marginal palpebral conjunctiva (also known as “lid wiper”). However, the underlying neurosensory mechanism
remains elusive. We recently found that a population of primary sensory neurons defined by the expression of
MrgprD selectively innervates the lid wiper and is sensitive to shear force. This proposal aims to determine
whether MrgprD-expressing sensory fibers mediate ocular mechanosensation and regulate lacrimation. In Aim
1, we will characterize the innervations and mechanosensitivity of MrgprD-expressing sensory fibers in the lid
wiper. Using genetic labeling and axonal tracing approaches, we will perform detailed anatomical analysis of
organization and terminal ultrastructure of MrgprD-expressing sensory fibers in the lid wiper. In addition, we will
test whether MrgprD-expressing sensory fibers in the lid wiper can be activated by shear force by conducting ex
vivo calcium imaging. These studies will shed light on the role of MrgprD-expressing sensory fibers in ocular
mechanosensation. In Aim 2, we will further determine whether MrgprD-expressing sensory fibers sense shear
force during eye movements. We will determine whether genetic ablation or pharmacological silencing of
MrgprD-expressing neurons alleviates the ocular mechanosensation induced by enhanced shear force. This
study will provide insight on the neurosensory mechanism of the lid wiper mechanosensation. In Aim 3, we will
determine whether the lid wiper mechanosensation regulates lacrimation to maintain the lubrication of the ocular
surface. Specifically, we will examine whether ablation of MrgprD-expressing sensory fibers affects basal
lacrimation and mechanically-induced lacrimation. Furthermore, we will test whether chemogenetic activation of
MrgprD-expressing sensory fibers in the lid wiper promotes lacrimation. Finally, we will determine whether
pharmacological activation of MrgprD-expressing sensory fibers is a potential therapeutic strategy for promoting
lacrimation under dry eye conditions. These studies will reveal the neural basis of ocular mechanosensation
associated with physiological tear evaporations and pathological dryness of the ocular surface, which will have
a significant impact in our understanding of ocular mechanosensation as a protective mechanism and its clinical
implication in dry eye treatments.

## Key facts

- **NIH application ID:** 10463561
- **Project number:** 5R01EY024704-08
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Qin Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $470,405
- **Award type:** 5
- **Project period:** 2014-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463561

## Citation

> US National Institutes of Health, RePORTER application 10463561, The Neural Basis of Ocular Sensations (5R01EY024704-08). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10463561. Licensed CC0.

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