Self-Assembled Sulfated Hyaluronan Coating Modulates Transforming Growth Factor-Beta1 Penetration for Corneal Scarring Alleviation

Abstract

Corneal scarring caused by epithelial-stromal injury impairs corneal transparency and visual acuity. Excess secretion of transforming growth factor-beta 1 (TGF-β1), which promotes wound closure, penetrates the corneal stroma via defects in the epithelial basement membrane and induces the differentiation of corneal fibroblasts to myofibroblasts, leading to scar formation. Modulating TGF-β1 penetration might alleviate corneal scar formation and restore transparency. In this study, sulfated hyaluronan (sHA) coatings were self-assembled above wounded corneal stroma to modulate TGF-β1 penetration, and their ability to alleviate corneal scarring was investigated. The formation of sHA coatings was rapid (within 30 s), and the high-sulfated hyaluronan coating efficiently blocked penetration by TGF-β1 and reduced the concentration of TGF-β1 in the corneal stroma. Further investigation showed that the ability of TGF-β1 to induce differentiation of corneal fibroblasts into myofibroblasts was inhibited by sHA binding. Evaluation of corneal scarring with sHA coating in a rabbit model of lamellar resection indicated that a sHA (high sulfation) coating effectively reduced scar formation. Immunohistochemical staining of α-smooth muscle actin and optical coherence tomography of the anterior segment showed minimal scar tissue formation in the sHA group. This work presents a promising alternative to alleviate scarring in corneal epithelial-stromal injury.