Overview of CFTR activators and their recent studies for dry eye disease: a review

Area of Science:

• Ocular surface physiology
• Pharmacology of secretory epithelial cells
• Dry eye disease therapeutics

Background:

• Cystic fibrosis transmembrane conductance regulator (CFTR) is activated by cAMP signaling in ocular surface epithelia.
• CFTR activation promotes fluid secretion on ocular surfaces in mice and humans.
• Dry eye disease is a prevalent condition with limited effective treatments.

Purpose of the Study:

• To summarize small molecule CFTR activators for dry eye treatment.
• To outline pharmacological testing and structural optimization of these activators.
• To highlight CFTR activators as a potential new strategy for dry eye disease.

Main Methods:

• Review of chemical structures of small molecule CFTR activators.
• Summary of pharmacological activity testing in dry eye models.
• Analysis of structure-activity relationships for optimization.

Main Results:

• Various small molecule CFTR activators with diverse chemical scaffolds have been identified.
• Pharmacological testing demonstrates the efficacy of these activators in preclinical models.
• Structural optimization has led to improved potency and drug-like properties.

Conclusions:

• Small molecule CFTR activators represent a promising therapeutic avenue for dry eye disease.
• Targeting CFTR offers a novel mechanism to restore ocular surface hydration.
• Further development of CFTR activators could lead to new treatments for dry eye patients.