The effect of TC14012 on alkali burn-induced corneal neovascularization in mice.
OBJECTIVE
To observe the effect of TC14012 (a CXCR4 antagonist and CXCR7 agonist) on alkali burn-induced corneal neovascularization (CNV) in a mouse model.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, PR China.
Minqian
M
Shen
Fei
F
Yuan
Jing
J
Jin
Yuanzhi
Y
Yuan
D000818:Animals; D002057:Burns, Chemical / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D003228:Conjunctiva / Q000187:drug effects; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D005126:Eye Burns / Q000139:chemically induced*; D005786:Gene Expression Regulation / Q000502:physiology; D056965:Injections, Intraocular; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D054387:Receptors, CXCR / Q000819:agonists* / Q000235:genetics; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics; D012972:Sodium Hydroxide; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
C514936:CXCR4 protein, mouse; C501897:Cmkor1 protein, mouse; D009842:Oligopeptides; D012333:RNA, Messenger; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; C504129:TC14012; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D012972:Sodium Hydroxide; D020782:Matrix Metalloproteinases