Nanoparticle-mediated inhibition of Yes-associated protein prevents corneal scarring after traumatic injury

Corneal scars develop during the regenerative process following traumatic injuries. Verteporfin (VP), a Yes-associated protein (YAP) inhibitor, has shown promise as an antifibrotic agent, but its application to the ocular surface is limited by unfavorable physicochemical properties. Here, we developed the hyaluronic acid-verteporfin nanoparticles (HA-VP NPs) to increase the apparent solubility of VP and prolong residence on the eye, aiming to promote corneal regeneration and prevent scar formation following injuries. The HA-VP NPs effectively prevented not only the transformation of corneal stromal cells into myofibroblasts, but also the epithelial-mesenchymal transition of epithelial cells by inhibiting the translocation of YAP into the nucleus. HA-VP NPs interacted with CD44 receptors, facilitating endocytosis in corneal stromal cells and contributing to prolonged residence time in corneal defects. In a rat anterior lamellar keratoplasty model, the HA-VP NPs were retained on corneal defects for at least 4 hours, resulting in excellent corneal regeneration and significant reduction in scarring.