The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China.
Department of Laboratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Immunology. 2024 Sep;173(1):141-151. doi: 10.1111/imm.13818. Epub 2024 May 28.
Retinopathy of prematurity (ROP) is a retinal disease-causing retinal neovascularization that can lead to blindness. Oxygen-induced retinopathy (OIR) is a widely used ROP animal model. Icariin (ICA) has anti-oxidative and anti-inflammation properties; however, whether ICA has a regulatory effect on OIR remains unclear. In this study, ICA alleviated pathological neovascularization, microglial activation and blood-retina barrier (BRB) damage in vivo. Further results indicated that endothelial cell tube formation, migration and proliferation were restored by ICA treatment in vitro. Proteomic microarrays and molecular mimicry revealed that ICA can directly bind to hexokinase 2 (HK2) and decrease HK2 protein expression in vivo and in vitro. In addition, ICA inhibited the AKT/mTOR/HIF1α pathway activation. The effects of ICA on pathological neovascularization, microglial activation and BRB damage disappeared after HK2 overexpression in vivo. Similarly, the endothelial cell function was revised after HK2 overexpression. HK2 overexpression reversed ICA-induced AKT/mTOR/HIF1α pathway inhibition in vivo and in vitro. Therefore, ICA prevented pathological angiogenesis in OIR in an HK2-dependent manner, implicating ICA as a potential therapeutic agent for ROP.
早产儿视网膜病变（ROP）是一种视网膜疾病，可导致视网膜新生血管形成，从而导致失明。氧诱导的视网膜病变（OIR）是一种广泛使用的 ROP 动物模型。淫羊藿苷（ICA）具有抗氧化和抗炎特性；然而，ICA 是否对 OIR 具有调节作用尚不清楚。在这项研究中，ICA 减轻了体内病理性新生血管形成、小胶质细胞激活和血视网膜屏障（BRB）损伤。进一步的结果表明，ICA 处理可在体外恢复内皮细胞管形成、迁移和增殖。蛋白质组微阵列和分子模拟表明，ICA 可直接与己糖激酶 2（HK2）结合，并减少体内和体外的 HK2 蛋白表达。此外，ICA 抑制 AKT/mTOR/HIF1α 通路的激活。体内过表达 HK2 后，ICA 对病理性新生血管形成、小胶质细胞激活和 BRB 损伤的作用消失。同样，过表达 HK2 后内皮细胞功能得到修正。HK2 过表达逆转了体内和体外 ICA 诱导的 AKT/mTOR/HIF1α 通路抑制。因此，ICA 以依赖 HK2 的方式防止了 OIR 中的病理性血管生成，提示 ICA 可能是 ROP 的一种潜在治疗剂。
