# A transient receptor potential vanilloid 1-dependent corneal–trigeminal neuroinflammatory circuit promotes corneal neuropathy

## TL;DR

The study reveals a neuroinflammatory pathway involving TRPV1 channels that contributes to corneal neuropathy in dry eye disease, offering new therapeutic targets.

## Contribution

The paper identifies a TRPV1-dependent corneal–trigeminal neuroinflammatory circuit as a novel mechanism in corneal neuropathy.

## Key findings

- TRPV1 activation in dry eye disease triggers neuroinflammation and macrophage reactivity in the trigeminal ganglion.
- Blocking substance P reverses TRPV1-driven corneal nerve abnormalities.
- TRPV1 overactivation alone can cause corneal nerve degeneration and neuroinflammation.

## Abstract

Corneal neurosensory abnormalities cause pain and discomfort in ocular surface disease, yet their pathophysiology is poorly understood. Here we show that in a mouse dry eye model, the ocular (over)activation of transient receptor potential vanilloid 1 (TRPV1) channels in response to tear deficiency and tissue damage promotes neuroinflammatory gene expression and macrophage reactivity in the trigeminal ganglion, where the cornea-innervating sensory neurons are located. This is accompanied by ocular surface macrophage activation, impaired corneal sensitivity to mechanical and non-TRPV1-mediated chemical stimulation, reduced corneal nerve density and the sensitization of ocular TRPV1 channels, thus establishing a vicious neurosensory cycle. Isolated corneal TRPV1 activation without ocular desiccation recapitulates macrophage reactivity, corneal nerve degeneration and trigeminal neuroinflammation, whereas the ocular substance P blockade reverts most of the TRPV1-driven corneal neurosensory abnormalities. Our study identifies a corneal–trigeminal axis that facilitates corneal neurosensory dysfunction and suggests potential targets for the treatment of ocular surface disease-associated corneal neuropathy.

The cornea needs to stay healthy for good vision. It has many nerve fibers that help protect the eye by sensing changes and triggering immune responses. However, problems with these nerves, known as corneal neuropathy, are common in conditions such as dry eye disease (DED), where tears are insufficient or poor in quality. Researchers explored how DED affects corneal nerves and the role of a protein called TRPV1. The researchers used mice to study DED by removing a tear gland from one eye, creating a model of unilateral (one-sided) DED. They found that TRPV1 is crucial in spreading inflammation and nerve damage from the affected eye to the other eye. They also discovered that blocking a substance called substance P, which is released during nerve activation, can reduce nerve damage.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.