Oncotarget

Research Papers:

Subconjunctival injection of antagomir-21 alleviates corneal neovascularization in a mouse model of alkali-burned cornea

Yun Zhang, Ting Zhang, Xiaoyun Ma and Jun Zou _

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Oncotarget. 2017; 8:11797-11808. https://doi.org/10.18632/oncotarget.14370

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Abstract

Yun Zhang1,2, Ting Zhang3, Xiaoyun Ma4, and Jun Zou1,3

1Department of Ophthalmology, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai, China

2Department of Plastic Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

3Shanghai Sixth People’s Hospital Affiliated to JiaoTong University, Shanghai, China

4Department of Ophthalmology, Guanghua Integrative Medicine Hospital, Shanghai, China

Correspondence to:

Jun Zou, email: [email protected]

Xiaoyun Ma, email: [email protected]

Keywords: microRNA sequencing, antagomir-21, alkali-burned cornea, corneal neovascularization, Sprouty

Received: July 22, 2016    Accepted: December 15, 2016    Published: December 30, 2016

ABSTRACT

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.


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