The Effect of TC14012 on Alkali Burn-Induced Corneal Neovascularization in Mice

<b><i>Aims:</i></b> To observe the effect of TC14012 (a CXCR4 antagonist and CXCR7 agonist) on alkali burn-induced corneal neovascularization (CNV) in a mouse model. <b><i>Methods:</i></b> CNV was induced in vivo by alkali burns on the corneas of BALB/c mice. A total of 54 mice treated with alkali burns were randomly divided into 3 groups, each of which received one of the following treatments: bilateral subconjunctival injections of TC14012 for 3 consecutive days, bilateral subconjunctival injections of balanced saline (BS) for 3 consecutive days or no treatment (blank control). The areas of CNV were measured on days 3, 7 and 14 after the alkali burns. CXCR4, CXCR7, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP) mRNAs were detected and quantified by real-time reverse transcription PCR on days 7 and 14. Additionally, the expression of the proteins CXCR4, CXCR7, VEGF, β-arrestin 2, total ERK1/2 and phospho-ERK1/2 was determined by Western blotting. <b><i>Results:</i></b> On day 7 after the alkali burns, the CNV area, VEGF, MMP-2 and MMP-9 mRNA levels, and VEGF, β-arrestin 2 and phospho-ERK1/2 protein levels were increased in the TC14012 group compared with the nontreatment and BS groups. However, on day 14, the CNV area, CXCR4, CXCR7, VEGF, MMP-2 and MMP-9 mRNA levels, and the CXCR4, CXCR7, VEGF and β-arrestin 2 protein levels were significantly decreased in the TC14012 group. <b><i>Conclusions:</i></b> TC14012 initially enhanced alkali burn-induced CNV but reduced CNV in later stages. In addition to CXCR4, CXCR7 is involved in the pathogenesis of CNV.