Abstract:

Objective To determine the role of chemokine (C-X-C motif) ligand 12 (CXCL12)/chemokine (C-X-C motif) receptor 4 (CXCR4) in inflammatory corneal hemangiogenesis, and to study the relationship between VEGF-A family and CXCL12 / CXCR4 in the corneal neovascularization. Design Experimental study. Participants Twenty-four mice. Methods Corneal hemangiogenesis was induced by placing three 11-0 nylon sutures in the corneal intrastromal. Mice were divided into three groups (8 mice in saline control group, AMD3100 subconjunctival injection group and suture model group each). Immunohistochemical method was used to investigate the CXCR4 expression. Fluorescence quantitative PCR and Western blot were used to investigate the expression of CXCL12 / CXCR4 and VEGFA family. Immunofluorescence assay was used to measure the area of new blood vessels invasion. Main Outcome Measures The expression of CXCR4, CXCL12/CXCR4 and VEGFA family, and the area of new blood vessels invasion. Results CXCL12/CXCR4 mRNA and protein expression levels increased markedly in suture-induced corneal neovascularization (CXCL12: 0.40±0.01 μg, CXCR4: 0.40±0.03 μg, VEGF-A: 0.99+0.39 μg, VEGFR-1: 0.91+0.45 μg) and decreased in the AMD3100 group (CXCL12: 0.20±0.02 μg, CXCR4: 0.28±0.07 μg, VEGF-A: 0.64+0.20 μg, VEGFR-1: 0.64+0.25 μg). Hemangiogenesis was captured in immunofluorescence images and the area was shown to be markedly increased in the suture model group (1.00±0.22),  which was consistent with the increasing expression of the CXCL12/CXCR4. Conclusion CXCL12/CXCR4 regulates hemangiogenesis in suture-induced corneal hemangiogenesis. AMD3100 may be a novel therapeutic target for the prevention of corneal neovascularization.

Key words: neovascularization, CXCR4/CXCL12, vascular endothelial growth factor