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.
Highlights
Alkali burn injuries to the eye frequently lead to corneal neovascularization resulting in loss of corneal transparency and blindness
An alkali-burned cornea is an outstanding model to observe the sprouting of blood vessels and to test antiangiogenic therapies
We demonstrated that corneal neovascularization development induced by an alkali burn was accompanied by an elevation of miR-21 along with an increased expression of vascular endothelial growth factor (VEGF)-A
Summary
Alkali burn injuries to the eye frequently lead to corneal neovascularization resulting in loss of corneal transparency and blindness. MiRNAs including miR-205 [3, 4], miR-204 [5] and miR-424 [6] have been associated with corneal wound healing. It has been reported that the treatment of diabetic organ-cultured corneas with miR-146a antagomir significantly enhanced cell migration and normalized epithelial wound healing [7]. MiRNAs regulate gene expression at the posttranscriptional level and play crucial roles in angiogenesis [8, 9]. As such, they may have a role in regulating corneal neovascularization. The identification of miRNAs as markers and modulators of www.impactjournals.com/oncotarget corneal angiogenesis in various pathological conditions will provide us with gene-based therapies for corneal blindness
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