A Study by UMH Neurosciences Reveals Light-Activated Molecule Could Non-Invasively Relieve Dry Eye Pain

Research led by the Institute of Neurosciences (IN), a joint centre of the Spanish National Research Council (CSIC) and the Miguel Hernández University (UMH), has tested an experimental molecule activated by blue light that could alleviate dry eye symptoms.

The compound, named DENAQ, is applied for the first time to the sensory nerves of the cornea, the transparent layer covering the front of the eye. In animal models, it has shown to "reduce excessive activity of these nerves without affecting essential functions like blinking."

Additionally, as detailed by the IN CSIC-UMH in a statement, "this is the first time it has been demonstrated that a photosensitive molecule can control corneal nerve activity using light." "This finding paves the way for new non-invasive light-based treatments, known as optopharmacology," it noted.

Dry eye is a disease of the ocular surface that occurs when the eyes do not produce enough tears or the tears are of poor quality, causing symptoms such as dryness, burning, itching, a gritty sensation, and blurred vision.

In Spain, according to a recent report, dry eye disease could affect 30% of the population, with an increase in cases among those under 30 years old. In this regard, DENAQ is a photoactive compound originally developed to confer light sensitivity to nerve cells, such as retinal ganglion cells, which send visual information to the brain for vision.

In this new work, the IN team applies it for the first time to the sensory nerves of the cornea, representing a "novelty" in its experimental use. The electrical activity of the nerve endings that detect cold in the cornea is "essential" for maintaining ocular surface health, as it regulates blinking and tear production. However, when this activity becomes excessive, as in dry eye cases, it can cause persistent discomfort.

A new study led by researcher Víctor Meseguer, who co-directs the Ocular Neurobiology Laboratory at IN, demonstrates that a light-sensitive molecule called DENAQ can modulate this nerve hyperactivity by applying blue light, reducing abnormal signals without eliminating normal cold sensitivity.

"The most interesting aspect is that the light does not block the function of these nerves but restores it to normal. In dry eye conditions, the endings are firing excessively, and in the presence of the optopharmaceutical with light, we manage to bring their activity back to healthy levels," explained Meseguer.

The work, published in the 'British Journal of Pharmacology', shows that DENAQ acts as a chemical switch: by changing shape under blue light, it modulates the ion channels of corneal neurons and reduces their excitability.

The experiments, conducted in guinea pig and rat models, confirmed that this effect persists even in corneas with induced dryness, without altering the normal response to cold stimuli.

The use of DENAQ allows precise control of peripheral nerve activity through a light stimulus. This ability to adjust nerve excitability offers unprecedented control in sensory structures like the cornea, where protective function must remain active while avoiding overstimulation that causes pain or irritation.

The possibility of acting only on the affected area and reversibly makes this strategy "a promising alternative to conventional pharmacological treatments, which often present side effects or loss of sensitivity," according to IN CSIC-UMH.

Similarly, the study provides a "new understanding" of the molecular mechanisms of corneal receptors. Researchers found that the molecule enters nerve endings through P2X3 channels, structures not previously described with this role in the cornea, paving the way "for the design of future more specific photosensitive drugs."

This approach falls within the emerging field of optopharmacology, which allows modulation of nervous system activity using light without genetic manipulation, unlike optogenetics.

"This is the first time it has been demonstrated that a photosensitive molecule can control corneal nerve activity with light. It is a very solid proof of concept for developing therapeutic strategies based on optopharmaceuticals," highlighted David Ares, the first author of the article.

In this context, Meseguer emphasized that "these results reinforce" the idea that peripheral nerve activity can be controlled "locally, precisely, and reversibly, using light-sensitive drugs" and that, "in the future, it could help alleviate symptoms of dry eye or other peripheral neuropathies."

The DENAQ molecule was synthesized in collaboration with Professor Richard H. Kramer's group at the University of Berkeley (California), an "international reference" in the development of photosensitive compounds that had characterized the photodynamic properties of the molecule and its activity in retinal ganglion cells, according to IN CSIC UMH.