PHARMACEUTICAL | DRY EYE

Understanding Dry Eye

Dry Eye Disease:
Disruption of Ocular Surface Homeostasis

Dry eye disease (DED) is a complex condition with multiple etiologies, all of which lead to a tear deficiency, which is a reduction in tear volume and/or altered tear composition.^1,2

Tear deficiency perpetuates the vicious cycle of DED, which involves tear instability and hyperosmolarity, corneal and conjunctival cell death, inflammation, goblet cell loss, and neurosensory abnormalities.^1,2

Overview of DED Treatment Modalities

The current DED prescription treatment landscape includes ocular and nasally administered drugs that make up four drug classes: anti-inflammatory, immunomodulatory, anti-evaporative, and neuroactivation.^3-6

Neuroactivators are drugs that unilaterally upregulate signaling and activity.⁷ In tear production, a neuroactivator activates the trigeminal nerve of the lacrimal functional unit (LFU) to coordinate innervation of secretory glands (lacrimal glands, goblet cells, and meibomian glands), leading to the release of important tear components.^8,9

This LFU activation can occur through either the nasal or ocular pathways, involving different receptors.⁸ Presently, the only neuroactivator approved for treating dry eye is administered through the nasal cavity.⁷

Corneal TRPM8 Thermoreceptors,
A Novel Target for Tear Production

Corneal transient receptor potential (TRP) ion channels, which respond to a wide array of environmental stimuli, play a role in various physiological and pathophysiological processes.^10,11 These channels are being explored as potential therapeutic targets for dry eye.

Transient Receptor Potential Melastatin 8 (TRPM8) ion channels are expressed on corneal cold thermosensory neurons and are responsible for regulating tear production.^12-14

Review our infographic and video for more information about TRPM8.