The cornea–trigeminal axis: potassium channels as master regulators of ocular surface homeostasis and sensory transduction

Introduction The cornea and trigeminal ganglion (TG) form an integrated sensory network that monitors ocular surface integrity and mediates protective responses to environmental stimuli. Potassium (K + ) channels are central regulators along this cornea–TG axis, controlling membrane excitability, sensory thresholds, epithelial repair, stromal remodeling, and inflammatory signaling. Methods This review synthesizes current knowledge of K + channel distribution, function, and dysfunction within the cornea–TG axis, based on findings from animal, ex vivo, and human tissue models. Results In corneal epithelial and stromal cells, channels such as Kir4.1 and K Ca 3.1 modulate membrane potential and intracellular Ca 2+ dynamics, coordinating wound healing and fibrotic responses. In sensory neurons, K v , K 2P , and K Ca channels cooperate with TRP channels to integrate mechanical, thermal, and chemical inputs, setting firing thresholds and shaping nociceptive signaling. Dysregulation of these channels contributes to dry eye disease, corneal neuropathic pain, and impaired epithelial repair, highlighting their mechanistic and translational significance. Discussion Despite advances in animal and ex vivo models, species-specific variability, limited human tissue validation, and a lack of cell-type resolution constrain current understanding. Future studies leveraging physiologically relevant models, selective pharmacological tools, and longitudinal analyses are critical to define dynamic K + channel regulation and to guide the development of novel therapeutic strategies for ocular surface disease.