A new study published in Ocular Surface has explored an innovative mechanism for modulating tear production by activating the transient receptor potential melastatin 8 (TRPM8) channel in corneal sensory nerves. The approach highlights the potential of neurostimulation-based strategies to address the underlying pathophysiology of dry eye disease (DED), particularly in patients unresponsive to conventional anti-inflammatory therapies.
The TRPM8 ion channel, predominantly expressed in cold-sensitive sensory neurons, is known to regulate ocular surface homeostasis. The authors used both in vivo and ex vivo methods in a murine model to elucidate the role of TRPM8 in tear secretion. Application of the TRPM8 agonist cryosim-3 (C3) resulted in significant increases in basal tear production. Electrophysiological recordings revealed that C3 stimulated corneal cold thermoreceptor activity, suggesting that TRPM8 activation enhances tear secretion via a neurogenic reflex arc.
Importantly, there were no pro-inflammatory effects observed in response to TRPM8 stimulation, making this a potentially safer long-term approach compared to some existing therapies.
From a clinical standpoint, the findings present TRPM8 as a promising therapeutic target for patients with aqueous-deficient DED. The selective stimulation of corneal cold receptors to boost natural tear production could offer a physiological, non-immunosuppressive treatment pathway, potentially addressing both symptoms and tear film instability. Unlike artificial tears or anti-inflammatory agents, TRPM8 agonists may provide more durable symptom relief by enhancing the eye’s own secretory mechanisms.
The study opens avenues for the development of TRPM8-based topical agents, nasal sprays, or neuromodulatory devices that can be personalized based on corneal nerve density and function. While preliminary safety and efficacy results in animal models are encouraging, translational studies in humans will be essential to determine optimal dosing, delivery methods, and long-term outcomes.
