Li Tao, Wu Xiaoli, Huang Yi, Tang Juan, Zhang Yu, Du Yangrui, Du Zhiyu
Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Biomater Res. 2025 May 14;29:0202. doi: 10.34133/bmr.0202. eCollection 2025.
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) with controlled drug release, inflammation targeting, and good biocompatibility for corneal haze treatment. In this study, we discovered that Tet@TiO and tetrandrine (Tet), but not TiO, displayed a characteristic absorption peak at 282 nm. Three weeks after transepithelial photorefractive keratectomy surgery, the Tet@TiO 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 groups, the α-smooth muscle actin, connective tissue growth factor, and type III collagen fibers in the Tet@TiO group decreased more significantly after fluorometholone eye drop and Tet treatment, indicating that Tet@TiO can effectively inhibit the expression of these inflammatory factors during corneal haze formation. Moreover, Tet@TiO showed good, sustained antibacterial properties. More importantly, we found that Tet@TiO 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.
角膜表面屈光手术后，预防和治疗角膜混浊至关重要。然而，应用传统抗炎皮质类固醇后产生的高眼压已引起广泛关注。因此，我们合成了一种具有控释药物、炎症靶向性和良好生物相容性的多功能纳米药物（Tet@TiO）用于角膜混浊治疗。在本研究中，我们发现Tet@TiO和粉防己碱（Tet）在282nm处显示出特征吸收峰，而TiO没有。经上皮准分子激光角膜切削术后三周，Tet@TiO组的细胞核体积、角膜细胞水肿、I型和III型胶原纤维表达显著降低，细胞器形态正常，胶原纤维排列有序。与对照组和TiO组相比，Tet@TiO组在使用氟米龙滴眼液和Tet治疗后，α-平滑肌肌动蛋白、结缔组织生长因子和III型胶原纤维下降更为显著，表明Tet@TiO在角膜混浊形成过程中能有效抑制这些炎症因子的表达。此外，Tet@TiO表现出良好的持续抗菌性能。更重要的是，我们发现Tet@TiO可以通过调节角膜表面屈光手术后的炎症PI3K-AKT-Bax/Bcl-2信号通路，有效下调磷脂酰肌醇3激酶（PI3K）、蛋白激酶B（AKT）和B细胞淋巴瘤-2（Bcl-2）的表达，并上调Bcl-2相关X蛋白（Bax）的表达，从而通过减少炎症因子的表达有效预防和治疗角膜混浊。
