Zhang Yun, Zhang Ting, Ma Xiaoyun, Zou Jun
Department of Ophthalmology, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
Department of Plastic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Oncotarget. 2017 Feb 14;8(7):11797-11808. doi: 10.18632/oncotarget.14370.
Corneal neovascularization may result in loss of corneal transparency and blindness. However, developing successful and inexpensive medical treatments for corneal neovascularization remains an unresolved issue. Recently, several studies have implicated miRNA functions in the regulation of cornea homeostasis. This study aimed to identify the miRNA expression profile in the neovascularized cornea after an alkali burn and to investigate the related underlying mechanisms. Here, alkali-burned corneas and matched normal tissues were pooled to perform miRNA sequencing. MiR-21 in alkali-burned cornea showed the greatest increment of abundance at 4 and 7 d after injury compared to the healthy cornea. The miR-21 expression was positively correlated with both the mRNA and protein level of key angiogenic factors including vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor-1α (HIF-1α). At 2 and 8 d after alkali burn, the mice received subconjunctival injections of antagomir-21 (1 or 5 nmol per injection). The injection of antagomir-21 (5 nmol) inactivated miR-21 and attenuated neovascularization progression by inhibiting the expression of VEGF-A and HIF-1α. Western blot analysis of the corneas demonstrated that antagomir-21 restored Sprouty 2/4 expression and silenced p-ERK activation. Therefore, these data reveal that antagomir-21 ameliorates the progression of corneal neovascularization likely via Sprouty 2/4-mediated inactivation of p-ERK. Delivery of antagomir-21 might be a potential therapeutic approach to prevent or treat visual loss caused by corneal neovascularization.
角膜新生血管化可能导致角膜透明度丧失和失明。然而，开发成功且廉价的角膜新生血管化医学治疗方法仍是一个未解决的问题。最近，多项研究表明微小RNA（miRNA）在角膜稳态调节中发挥作用。本研究旨在确定碱烧伤后新生血管化角膜中的miRNA表达谱，并研究相关的潜在机制。在此，将碱烧伤的角膜和匹配的正常组织汇集起来进行miRNA测序。与健康角膜相比，碱烧伤角膜中的miR-21在损伤后4天和7天丰度增加最为显著。miR-21表达与包括血管内皮生长因子（VEGF）-A和缺氧诱导因子-1α（HIF-1α）在内的关键血管生成因子的mRNA和蛋白水平均呈正相关。碱烧伤后2天和8天，小鼠接受结膜下注射抗miR-21（每次注射1或5 nmol）。注射抗miR-21（5 nmol）可使miR-21失活，并通过抑制VEGF-A和HIF-1α的表达减轻新生血管化进程。对角膜进行的蛋白质印迹分析表明，抗miR-21恢复了Sprouty 2/4的表达并使p-ERK激活沉默。因此，这些数据表明抗miR-21可能通过Sprouty 2/4介导的p-ERK失活改善角膜新生血管化进程。抗miR-21的递送可能是预防或治疗角膜新生血管化所致视力丧失的一种潜在治疗方法。
