A non-penetrating colanic acid eye drops with anti-inflammatory and pro-repair functions for dry eye disease.

Dry eye disease (DED) is a prevalent disorder driven by inflammation and tear film instability, yet current therapies have limitations. Here, we developed a novel eye drop based on colanic acid (CA), an exopolysaccharide secreted by Enterobacteriaceae, for DED treatment. CA was systematically compared with hyaluronic acid (HA), a clinically established artificial tear. CA displayed suitable viscosity, pH and osmolarity comparable to HA, alongside excellent biocompatibility and potent anti-inflammatory effects, suppressing TNF-α and IL-1β while upregulating IL-4 and IL-10. In BAK-induced DED rat and pig models, CA effectively restored tear secretion, corneal integrity, and goblet cell function, with efficacy comparable to or exceeding that of HA. Notably, CA does not penetrate the cornea, positioning it as a medical device. Transcriptomic analysis further revealed that CA suppresses key inflammatory pathways and promotes corneal epithelial repair, distinguishing it from HA, which acts primarily as a physical lubricant. Collectively, CA represents a next-generation artificial tear that combines the safety of a non-penetrating medical device with active anti-inflammatory and pro-repair activities, supporting its clinical translational potential for DED.