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 for more information about TRPM8.
References:
1. Bron AJ, de Paiva CS, Chauhan SK, et al. Ocul Surf. 2017;15(3):438-510.
2. Craig JP, Nelson JD, Azar DT, et al. Ocul Surf. 2017;15(4):802-812.
3. Gao D, Da Z, Yang K, Shi Y. Front Pharmacol. 2022;13:882803.
4. Semba CP, Gadek TR. Clin Ophthalmol. 2016;10:1083-1094.
5. Frampton JE. Drugs. 2022;82(14):1481-1488.
6. Sheppard JD, Evans DG, Protzko EE. Am J Manag Care. 2023;29(14 Suppl):S251-S259.
7. Wirta D, Vollmer P, Paauw J, et al. Ophthalmology. 2022;129(4):379-387.
8. Wirta DL, Senchyna M, Lewis AE, et al. Ocul Surf. 2022;26:166-173.
9. Wirta D, Torkildsen GL, Boehmer B, et al. Cornea. 2022;41(10):1207-1216.
10. Samanta A, Hughes TET, Moiseenkova-Bell VY. Subcell Biochem. 2018;87:141-165.
11. Zhang M, Ma Y, Ye X, Zhang N, Pan L, Wang B. Signal Transduct Target Ther. 2023;8(1):261.
12. Belmonte C, Gallar J. Invest Ophthalmol Vis Sci. 2011;52(6):3888-3892.
13. Yang S, Wu Y, Wang C, Jin X. Front Med (Lausanne). 2022;9:830853.
14. Yang TJ, Yu Y, Yang JY, et al. Ann Transl Med. 2022;10(15):839.