Mechanism effect of HMGB1-TLR4 and Müller cells in retinal angiogenesis

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Journal of ShanDong First Medical University&ShanDong Academy of Medical Sciences ›› 2021, Vol. 42 ›› Issue (5) : 362-368. DOI: 10.3969/j.issn.2097-0005.2021.05.007

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Sun Yuying¹, Xiao Ou², Huang Chunyu³

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Received	Published
2021-01-11	2021-05-25
Issue Date
2021-08-31

Abstract

Objective: To explore the role of HMGB1-TLR4 signal pathway and Müller cells in retinal neovascularization.Methods: The mice were divided into three groups: normoxic group, normal OIR model group and TLR4 gene knockout (TLR4 ^-/-) OIR model group. Retinal FITC-Dextran fluorescence perfusion and GS-isolectin B4 staining were used to evaluate the neovascularization. Immunofluorescence staining was used to observe the expression of HMGB1 in mouse retina, the co-expressions of HMGB1 and TLR4, and the co-expressions of TLR4 and GFAP. The mRNA expressions of HMGB1 in the retina of OIR mice in P12 and P17 groups were detected by PCR. Results: It was observed that the neovascularization area of P17 normal OIR mice was the largest, while that of TLR4 ^-/-OIR mice was relatively small, which suggested that TLR4 gene deletion could inhibit angiogenesis. The results of immunofluorescence staining showed that the expressions of HMGB1, TLR4 and GFAP in TLR4 ^-/-OIR mice were lower than those in normal OIR group. The results of PCR examination showed that the expression levels of HMGB1 in TLR4 ^-/-OIR mice at P12 and P17 were lower than those in normal OIR group. These results suggested that inhibition of HMGB1-TLR4 signal pathway could weaken the activation of Müller cells and reduce neovascularization.Conclusion: This study explores the mechanism of HMGB1-TLR4 activating Müller cells participating in neovascularization, and reveals the effect of HMGB1-TLR4 on retinal neovascularization by activating Müller cells. It is suggested that blocking HMGB1-TLR4 pathway can weaken the activity of Müller cells and provide a new method for the treatment of retinal neovascularization.

Key words

HMGB1/Toll like receptor 4/Müller cells/retinal neovascularization/oxygen induced retinopathy model

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Sun Yuying, Xiao Ou, Huang Chunyu.Mechanism effect of HMGB1-TLR4 and Müller cells in retinal angiogenesis[J]. Journal of ShanDong First Medical University&ShanDong Academy of Medical Sciences. 2021, 42(5): 362-368 https://doi.org/10.3969/j.issn.2097-0005.2021.05.007

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