Abstract
Preventing and treating corneal haze is essential after corneal surface refractive surgery. However, the high intraocular pressure that results after applying traditional anti-inflammatory corticosteroids has attracted great attention. Therefore, we synthesized a multifunctional nanomedicine (Tet@TiO(2)) with controlled drug release, inflammation targeting, and good biocompatibility for corneal haze treatment. In this study, we discovered that Tet@TiO(2) and tetrandrine (Tet), but not TiO(2), displayed a characteristic absorption peak at 282 nm. Three weeks after transepithelial photorefractive keratectomy surgery, the Tet@TiO(2) group displayed significant decreases in nuclear volume, corneal cell edema, type I and III collagen fiber expression, normal organelle morphology, and collagen fiber arrangement. Compared with those in the control and TiO(2) groups, the α-smooth muscle actin, connective tissue growth factor, and type III collagen fibers in the Tet@TiO(2) group decreased more significantly after fluorometholone eye drop and Tet treatment, indicating that Tet@TiO(2) can effectively inhibit the expression of these inflammatory factors during corneal haze formation. Moreover, Tet@TiO(2) showed good, sustained antibacterial properties. More importantly, we found that Tet@TiO(2) could effectively down-regulate the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and B-cell lymphoma-2 (Bcl-2) and up-regulate the expression of Bcl-2-associated X protein (Bax) by modulating the inflammatory PI3K-AKT-Bax/Bcl-2 signaling pathway after corneal surface refractive surgery to effectively prevent and treat corneal haze by reducing the expression of inflammatory factors.