Dry eye disease is a multifactorial condition characterized by an unstable tear film, which can lead to discomfort, visual disturbance, and potential damage to the ocular surface. Unlike traditional artificial tears that merely supplement the tear film externally, Diquas (diquafosol sodium) works by targeting the tear production process internally through a novel pharmacological mechanism.
The Role of the P2Y2 Receptor
The fundamental mechanism of Diquas centers on its action as a potent P2Y2 purinergic receptor agonist. These receptors are strategically located on various cells across the ocular surface, including the corneal and conjunctival epithelium, conjunctival goblet cells, and meibomian glands. When Diquas is instilled as an eye drop, it binds to and activates these P2Y2 receptors, triggering a cascade of intracellular events.
Activation of the P2Y2 receptor leads to an elevation of intracellular calcium ion concentrations within the ocular surface cells. This increase in intracellular calcium is the key signal that stimulates the secretion of the three essential components of the tear film: the mucin layer, the aqueous layer, and the lipid layer.
A Multi-faceted Approach to Tear Film Restoration
Mucin Secretion from Goblet Cells
The inner-most layer of the tear film, the mucin layer, is responsible for allowing the aqueous layer to spread evenly across the hydrophobic corneal surface. Diquas stimulates conjunctival goblet cells to secrete more mucin (specifically, MUC5AC), improving the wetting of the ocular surface. This increased mucin production enhances tear film stability and helps protect the cornea from desiccation.
Aqueous Fluid Production from Conjunctival Epithelium
Dry eye often results from a deficiency in the aqueous layer of the tear film. By activating P2Y2 receptors on the conjunctival epithelial cells, Diquas promotes the transport of fluid to the ocular surface. This direct stimulation of aqueous secretion from the conjunctiva, rather than the main lacrimal gland, is a crucial part of its mechanism, making it effective for patients with aqueous-deficient dry eye.
Lipid Secretion from Meibomian Glands
In addition to its well-established effect on mucin and aqueous secretion, research has also shown that Diquas stimulates lipid secretion from the meibomian glands. This mechanism, discovered more recently, suggests that Diquas can also address evaporative dry eye caused by meibomian gland dysfunction (MGD). By increasing lipid secretion, Diquas helps to form a more stable outer lipid layer, which prevents the excessive evaporation of the aqueous tears.
Comparing Diquas to Traditional Dry Eye Treatments
| Feature | Diquas (Diquafosol Sodium) | Traditional Artificial Tears (e.g., Sodium Hyaluronate) |
|---|---|---|
| Mechanism of Action | Activates P2Y2 receptors to stimulate natural secretion of mucin, aqueous, and lipids. | Lubricates and moisturizes the ocular surface by supplementing the tear film externally. |
| Tear Film Effect | Addresses all three components (mucin, aqueous, lipid) by promoting natural secretion. | Primarily replaces the aqueous layer; less effective at restoring the mucin and lipid layers. |
| Long-Term Benefits | Helps repair corneal epithelial damage and improve tear film stability over time. | Provides temporary relief of symptoms without addressing the underlying tear production issues. |
| Targeted Therapy | A physiological approach that directly stimulates tear components from native ocular surface cells. | A symptomatic approach that relies on exogenous lubrication. |
Clinical Efficacy and Safety Profile
Multiple clinical trials have confirmed the effectiveness and safety of Diquas for dry eye treatment. A Phase 2 trial demonstrated that Diquas significantly improved corneal and conjunctival staining scores compared to a placebo at four weeks. Long-term observational studies further showed that Diquas effectively improves subjective symptoms and objective signs, such as tear break-up time (TBUT), in patients with dry eye.
Reported adverse effects are typically mild and transient, with the most common being eye irritation or foreign body sensation shortly after instillation. These side effects generally diminish with continued use as the ocular surface heals. The medication is also rapidly metabolized on the ocular surface, minimizing systemic absorption and associated side effects.
Conclusion: A Shift Toward Restoring Natural Function
Diquas represents a significant advancement in dry eye management by moving beyond simple lubrication to address the fundamental instability of the tear film. Its unique mechanism, centered on activating the P2Y2 receptor, empowers the ocular surface to produce a balanced, healthy tear film from within. By stimulating the natural secretion of mucin, aqueous, and lipids, Diquas not only alleviates symptoms but also promotes the repair of the corneal epithelium, leading to sustained improvement for a wide range of dry eye patients. This targeted, physiological approach marks a new era in dry eye treatment, focusing on restoring natural ocular surface function rather than just masking symptoms.
For more detailed clinical information on Diquas, consult the following resource: Applications of Diquafosol Sodium in Ophthalmology.
