Chang Xue-Jiao, Guo Xiao-Xiao, Li Jing, Pu Qi, Li Xin-Yu
Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, Hubei 430030 China.
Department of Ophthalmology, Beijing Anzhen Hospital, Capital Medical University, 2 Anzhen Road, Chaoyang District, Beijing 100029, China.
Int Immunopharmacol. 2025 Feb 6;147:114025. doi: 10.1016/j.intimp.2025.114025. Epub 2025 Jan 11.
To explore the function of cyclopamine in corneal neovascularization and subsequent fibrosis after cornea alkali-burn injury.
In vivo, mice cornea were injured by NaOH, and then treated with cyclopamine, clodronate liposomes (CLO-LPS), and vehicle of cyclopamine separately by subconjunctival injections. Clinical features were observed and pathological characteristics were examined. In vitro, M1 macrophages (M1φ) and human umbilical vein endothelial cells (HUVECs) were co-cultured, and the abilities of proliferation, migration, and tube formation of HUVECs were detected under different interventions of M1φ.
Alkali-burn injury induced massive angiogenesis and decreased transparency of the cornea, along with numerous macrophages infiltration and Shh protein expression in the cornea. However, corneal neovascularization, macrophage infiltration, and Shh expression could suppressed by cyclopamine and CLO-LPS significantly. In addition, treatment with cyclopamine also reduced the expression of inflammatory factors (TNF-α, IL-6) and fibrosis factors (VIM, α-SMA). In vitro, M1φ promotes migration and tube formation of HUVECs by secreting Shh protein, which could be inhibited by cyclopamine.
Cyclopamine could suppress inflammation and angiogenesis of alkali-burned cornea, as well as subsequent fibrosis. The study reveals that cyclopamine suppresses corneal neovascularization in a dual mechanism of inhibiting macrophage infiltration and suppressing Shh signaling.
探讨环杷明在角膜碱烧伤损伤后角膜新生血管形成及后续纤维化过程中的作用。
在体内，用氢氧化钠损伤小鼠角膜，然后分别通过结膜下注射用环杷明、氯膦酸脂质体（CLO-LPS）和环杷明载体进行处理。观察临床特征并检查病理特征。在体外，将M1巨噬细胞（M1φ）与人脐静脉内皮细胞（HUVECs）共培养，并在M1φ的不同干预下检测HUVECs的增殖、迁移和管形成能力。
碱烧伤损伤诱导大量血管生成并降低角膜透明度，同时角膜中有大量巨噬细胞浸润和Shh蛋白表达。然而，环杷明和CLO-LPS可显著抑制角膜新生血管形成、巨噬细胞浸润和Shh表达。此外，用环杷明治疗还降低了炎症因子（TNF-α、IL-6）和纤维化因子（VIM、α-SMA）的表达。在体外，M1φ通过分泌Shh蛋白促进HUVECs的迁移和管形成，而环杷明可抑制这一过程。
环杷明可抑制碱烧伤角膜的炎症和血管生成以及后续纤维化。该研究表明，环杷明通过抑制巨噬细胞浸润和抑制Shh信号传导的双重机制抑制角膜新生血管形成。
