Rebuilding the autoimmune-damaged corneal stroma through topical lubrication

Corneal lubrication is the most common treatment for relieving the signs and symptoms of dry eye and is considered to be largely palliative with no regenerative functions. Here we challenge this notion by demonstrating that wetting the desiccated cornea of an aqueous-deficient mouse model with the simplest form of lubrication, a saline-based solution, is sufficient to rescue the severely disrupted collagen-rich architecture of the stroma, the largest corneal compartment that is essential to transparency and vision. At the single cell level we show that stromal keratocytes responsible for maintaining stromal integrity are converted from an inflammatory state into unique reparative cell states by lubrication alone, thus revealing the extensive plasticity of these cells and the regenerative function of lubricating the surface. We further show that the generation of a reparative phenotype is due, in part, to disruption of an IL1β autocrine amplification loop promoting chronic inflammation. Thus, our study uncovers the regenerative potential of topical lubrication in dry eye and represents a paradigm shift in our understanding of its therapeutic impact.