Li Zuohong, Chen Jianping, Lei Lei, Jiang Nan, Zhu Yanling, Jia Yu, Zhuo Yehong, Su Wenru
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Department of Pediatric Ophthalmology, Guangzhou Children's Hospital and Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Front Med (Lausanne). 2020 Nov 10;7:598056. doi: 10.3389/fmed.2020.598056. eCollection 2020.
Inflammation-induced angiogenesis plays a critical role in many eye diseases, and abnormal angiogenesis inhibition is regarded as a therapeutic approach. Here, we examined the effects of laquinimod on inflammatory corneal angiogenesis. Mouse model of corneal neovascularization was induced by NaOH. Laquinimod or control vehicle were topically applied to alkali-treated eyes twice a day for 10 days. Corneal neovascularization, infiltrating inflammatory cells, and the levels of chemokines, pro-inflammatory cytokines were assessed. RAW cells and human umbilical vein endothelial cells were used to further explore the underlying mechanisms of the effects of laquinimod on inflammation-induced angiogenesis. Topical administration of laquinimod to the injured corneas dramatically inhibited alkali-induced corneal neovascularization and decreased inflammatory cell (such as macrophage) infiltration in a corneal injury mouse model. Laquinimod significantly downregulated the expression of chemokines (monocyte chemotactic protein-1 and macrophage inflammatory protein-1), pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor-alpha), vascular endothelial growth factor, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 and apoptosis-associated speck-like protein containing C-terminal caspase-recruitment domain adaptor protein in both injured corneas and RAW cells. , laquinimod also dramatically inhibited the proliferation, migration and tube formation of human umbilical vein endothelial cells. Laquinimod inhibits inflammation-induced angiogenesis in the cornea. These results suggest that laquinimod is a potential new therapeutic option for corneal neovascularization and other angiogenesis-associated diseases.
炎症诱导的血管生成在许多眼部疾病中起关键作用，抑制异常血管生成被视为一种治疗方法。在此，我们研究了来氟米特对炎症性角膜血管生成的影响。用氢氧化钠诱导小鼠角膜新生血管模型。将来氟米特或对照载体每天两次局部应用于碱处理的眼睛，持续10天。评估角膜新生血管、浸润的炎症细胞以及趋化因子、促炎细胞因子的水平。使用RAW细胞和人脐静脉内皮细胞进一步探究来氟米特对炎症诱导的血管生成作用的潜在机制。在角膜损伤小鼠模型中，将来氟米特局部应用于受伤角膜可显著抑制碱诱导的角膜新生血管生成，并减少炎症细胞（如巨噬细胞）浸润。来氟米特显著下调受伤角膜和RAW细胞中趋化因子（单核细胞趋化蛋白-1和巨噬细胞炎性蛋白-1）、促炎细胞因子（白细胞介素-1β和肿瘤坏死因子-α）、血管内皮生长因子、含核苷酸结合寡聚化结构域样受体家族pyrin结构域的3以及含C端半胱天冬酶招募结构域衔接蛋白的凋亡相关斑点样蛋白的表达。此外，来氟米特还显著抑制人脐静脉内皮细胞的增殖、迁移和管腔形成。来氟米特抑制角膜炎症诱导的血管生成。这些结果表明，来氟米特是角膜新生血管生成和其他血管生成相关疾病潜在的新治疗选择。
