# Molecular, cellular, anatomical and neurobiological investigation of melanopsin-expressing corneal innervation, and its role in pain and photophobia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $390,000

## Abstract

Project Summary/Abstract:
 Corneal pain is an important mechanism to detect injury or damage, leading to protective responses to
limit injury if possible (tearing to remove a foreign object), initiate healing and protect the ocular surface
required for clear vision. When maladaptive, corneal pain can be so debilitating as to limit daily function,
dramatically reduce quality of life, and cause significant economic burden. There is considerable understanding
of the molecular and cellular underpinnings of pain perception in response to mechanical, chemical and
thermal stimuli, but the ability of light to influence pain (photoallodynia) after corneal injury is not well
understood. Accumulating evidence suggests photoallodynia uses melanopsin-expressing trigeminal ganglia
sensory neurons in addition to the classic retinal pathways, and that these same trigeminal ganglia neurons
contribute to corneal mechanical sensitivity. In this proposal, the knowledge gap concerning how this class of
trigeminal neurons contribute to corneal pain in normal and sensitized pathophysiological states in disease
models of corneal surface injury/dry eye disease, allergic eye disease and migraine will be addressed.
Preliminary data shows that melanopsin is expressed in both C-fiber (thermal and chemical) and Ad (pressure)
sensing mouse and human trigeminal neurons, some of which co-express CGRP. These melanopsin-
expressing neurons contribute to corneal mechanical and light sensitivity in normal and pathophysiological
conditions, and can respond to light ex vivo. Finally, the optic nerve is not required for behavioral measures of
light sensitivity in a model of trigeminal sensitization. Thus the hypothesis that melanopsin-containing corneal
trigeminal neurons function to modulate corneal mechanical sensitivity and light sensitivity by directly
contributing to corneal innervation, and use neuropeptides to modulate the corneal milieu to effect pain
perception and sensitization will be tested. Aim 1 will evaluate corneal innervation in adult and developmental
stages in mice lacking melanopsin-expressing trigeminal neurons to identify the mechanism by which these
mice have decreased corneal mechanical sensitivity. Aim 2 will evaluate the ability of melanopsin-expressing
corneal nerves to alter mechanical and light sensitivity by altering secretion of a representative neuropeptide in
normal and sensitized corneas in response to light. Aim 3 will evaluate which trigeminal ganglia neurons (C-
fiber of Ad) contribute to mechanical and light sensitivity in models of corneal disease, injury or sensitization.
The expected outcomes will elucidate molecular, cellular, anatomical and neurobiological mechanisms of
corneal innervation, pain and photoallodynia in normal and pathophysiological states.

## Key facts

- **NIH application ID:** 9863629
- **Project number:** 1R01EY030864-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Anna Matynia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,000
- **Award type:** 1
- **Project period:** 2020-02-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9863629

## Citation

> US National Institutes of Health, RePORTER application 9863629, Molecular, cellular, anatomical and neurobiological investigation of melanopsin-expressing corneal innervation, and its role in pain and photophobia (1R01EY030864-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9863629. Licensed CC0.

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