Corneal sensory nerve regulation of tear production through stimulation of transient receptor potential melastatin 8 (TRPM8) channel: A potential new approach for treating dry eye disease

The lacrimal functional unit (LFU) tightly controls the secretion of all tear components, thus playing a critical role in maintaining ocular surface homeostasis. Forming an exquisitely sensitive neural network across the ocular surface, corneal sensory nerves detect environmental stimuli (e.g., temp...

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Detalles Bibliográficos
Autores: Gallar, Juana, Pflugfelder, Stephen, Galor, Anat, Gupta, Preeya K., Hamrah, Pedram
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/421684
Acceso en línea:http://hdl.handle.net/10261/421684
https://api.elsevier.com/content/abstract/scopus_id/105011382752
Access Level:acceso abierto
Palabra clave:Corneal sensory nerves
Dry eye disease
TRP channels
TRPM8
Tear film
Trigeminal nerve
Descripción
Sumario:The lacrimal functional unit (LFU) tightly controls the secretion of all tear components, thus playing a critical role in maintaining ocular surface homeostasis. Forming an exquisitely sensitive neural network across the ocular surface, corneal sensory nerves detect environmental stimuli (e.g., temperature, chemicals, and mechanical pressure) through transient receptor potential (TRP) ion channels. Among these, TRP melastatin 8 (TRPM8) is a key regulator of basal tear production. Stimulated by the small temperature reductions and tear film osmolarity increases that arise due to evaporative cooling, TRPM8 activates the LFU, leading to increased basal tear production. Here, we focus on reviewing the topical ocular pathways within the LFU that regulate tear production. We describe the neural signaling underlying this regulation, with a focus on TRP channels and the central role of TRPM8 in basal tear production as elucidated through preclinical as well as limited clinical evidence. Lastly, we explore how augmenting the fundamental action of TRPM8 signaling through agonist stimulation may serve as a valuable new treatment option for dry eye disease.