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Lei Liu, Jian Liu, Andrew Dick; The Role of Toll-like Receptors in Corneal Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6191.
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To investigate whether TLR activation regulates VEGF production in macrophages and inhibits corneal angiogenesis.
Primary mouse bone marrow derived macrophages were treated with full range of TLR1-9 agonists for 24 h. Supernatants were collected for VEGF ELISA and NO assay. The mRNAs were extracted and VEGF expression was quantified by qPCR. Mouse aortic ring explants were cultured for 10 d before TLR ligands 1-9 were added into culture media. Vascular outgrowth was measured and compared between TLR ligands treated groups and control group after 7 d. Corneal angiogenesis was induced by corneal sutures on B6LY5 mice and sub-conjunctival administration of either poly I:C or water was performed at D3 and D7. Corneal angiogenesis was compared between the two groups clinically under surgical microscope and by immunofluorescent staining of LYVE-1 and CD31.
Production of VEGF in macrophages was reduced by TLR1, TLR2, TLR3, TLR4 and TLR9 engagements, while NO was only induced by TLR3, TLR4 and TLR9 activation. Interestingly, treatment of TLR3 ligand up-regulated VEGF mRNAs, while that of TLR9 down-regulated VEGF mRNAs of macrophages. TLR ligands treatment did not affect vascular outgrowth from aortic ring explants. Sub-conjunctival injection of poly I:C did not suppress corneal angiogenesis in mice.
TLRs especially TLR3 and TLR9 are capable of regulating VEGF in macrophages at both transcription and protein levels. TLRs can not regress vessel growth after establishment of angiogenesis, however, their roles in early stage of angiogenesis needs further investigation.
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