Topical lubrication restores dry eye corneal stroma by producing reparative keratocytesacripep promotes corneal regeneration in autoimmune mediated dry eye disease (Bulk RNA-Seq).

Topical lubrication is the most common remedy for relieving the signs and symptoms of dry eye. However, the therapeutic value of lubricating the ocular surface remains relatively unknown. Here we reveal the restorative properties of the simplest form of lubrication in a mouse model of autoimmune-mediated dry eye. We show topical treatment with PBS rescues corneal stromal architecture through restoring the basement membrane and collagen fiber alignment essential for maintaining corneal transparency. At the single cell level we show keratocytes exhibit significant plasticity under chronic injury, with continuous transition from a homeostatic to inflammatory state, and that lubrication converts these inflammatory cells to a unique reparative phenotype. We further identify IL1b-IL1R1-MAPK signaling as a key pathway driving keratocyte inflammation, and that disruption of the IL1b autocrine amplification loop by lubrication is sufficient to reprogram the inflammatory keratocytes towards the reparative state. Thus, our study underscores the regenerative potential of topical lubrication in dry eye, and reveals fibroblast-targeted therapies as a novel approach to restoring ocular surface health.