CXCL12/CXCR4 axis regulates neovascularization and lymphangiogenesis in sutured corneas in mice

Du,Ling‑Ling; Liu,Ping

doi:10.3892/mmr.2016.5179

CXCL12/CXCR4 axis regulates neovascularization and lymphangiogenesis in sutured corneas in mice

Authors:
- Ling‑Ling Du
- Ping Liu
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Affiliations: Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Published online on: April 25, 2016 https://doi.org/10.3892/mmr.2016.5179
Pages: 4987-4994
Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to determine the plausible functional role of chemokine (C‑X‑C motif) ligand 12 (CXCL12/chemokine (C‑X‑C motif) receptor 4 (CXCR4) in inflammatory corneal hemangiogenesis and lymphangiogenesis in vivo. Corneal hemangiogenesis and lymphangiogenesis were induced by placing an 11‑0 nylon suture in an intrastromal position. The expression levels of the vascular endothelial growth factor (VEGF) family, CXCL12 and CXCR4 in the corneas were investigated in the corneas using reverse transcription‑quantitative polymerase chain reaction and immunohistochemistry. Corneal hemangiogenic and lymphangiogenic responses were assessed by immunofluorescence using specific antibodies against cluster of differentiation 31 and lymphatic vessel endothelial hyaluronan receptor‑1. Subconjunctival injection of AMD3100 to the sutured corneas was also performed. CXCL12/CXCR4 mRNA and protein expression levels increased markedly in suture‑induced corneal neovascularization (CNV) and decreased with AMD3100 treatment. Hemangiogenesis and lymphangiogenesis were captured in images using immunofluorescence and were shown to be markedly increased with suture placement and reduced with AMD3100 treatment. VEGF‑A/VEGFR‑1 and VEGF‑C/VEGFR‑3 mRNA expression levels were upregulated in the suture placement and control groups, whereas the expression levels of all the factors were downregulated in the AMD3100 treatment group. The results from the present study demonstrated that CXCL12/CXCR4 interactions regulate hemangiogenesis and lymphangiogenesis in suture‑induced CNV. AMD3100 may be a novel therapeutic target for the prevention of blindness.

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