# Ocular Hyperalgesia in Dry Eye

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $384,438

## Abstract

Project Summary
 Dry eye disease (DE) is a multifactorial condition defined by signs of tear film instability and
symptoms of ocular irritation and blurred vision. Symptom relief is the primary reason DE patients seek
medical attention. However, topical eye treatments that reduce the signs of ocular inflammation often fail
to manage symptoms in moderate to severe cases and peripheral signs of DE do not reliably predict
disease severity. These findings suggest a critical role for CNS mechanisms in the development and
maintenance of ocular pain in severe cases of DE; however, little is known about central neural
processing of ocular signals that are relevant for symptomatic DE. Converging lines of evidence from
electrophysiological, molecular and anatomical approaches are applied in a rodent model for tear
deficiency, exorbital gland removal. The overall goals of this project are to determine mechanisms for
increased neural excitability of trigeminal brainstem neurons after persistent tear reduction and if neuron-
glia interactions contribute to altered neural processing and enhanced protective eye muscle reflexes.
Aim 1 develops a quantitative sensory testing (QST) protocol to characterize the encoding properties of
ocular trigeminal brainstem neurons in male and female rats. A novel recording and analysis method is
developed to assess squint-like activity in upper and lower portions of the orbicularis oculi muscle as a
measure of nociceptive behavior in anesthestized rats. Aim 2 determines if a “feed forward” pathway
connecting caudal with rostral trigeminal regions contributes to ocular hyperalgesia in DE. Aim 3
determines: a) if sensory signals that drive microglia activation do so by upregulating Toll-like and
purinergic P2x receptors, b) the distribution and localization neuroactive products by microglia (IL-1β,
BDNF) and their receptors on neurons and glia, and c) blockade of neuron-glia interactions alter the
properties of ocular-responsive neurons and evoked eyelid muscle responses in sham and DE male and
female rats. By combining neural recording and eye muscle activity with approaches that interfere with
microglia activation (purinergic receptors), inflammasome formation (NLRP3) and products of microglia
(IL-1β), this project will provide novel information on central mechanisms of ocular hypersensitivity in an
animal model for tear deficiency. The long-term goals of this project are to develop new approaches to
assess symptoms in moderate to severe cases of DE and to determine if targeting receptors for neuron-
microglia interactions has therapeutic potential to manage ocular hyperalgesia in DE.

## Key facts

- **NIH application ID:** 9917769
- **Project number:** 5R01EY028143-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** DAVID A BEREITER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $384,438
- **Award type:** 5
- **Project period:** 2017-09-30 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9917769

## Citation

> US National Institutes of Health, RePORTER application 9917769, Ocular Hyperalgesia in Dry Eye (5R01EY028143-04). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/9917769. Licensed CC0.

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