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Mengmeng Zhao, Yongguang Hu, Ying Yu, Qing Lin, Jianhua Yang, Shao Bo Su, Guo-Tong Xu, Tianshu Yang; Involvement of IL-37 in the Pathogenesis of Proliferative Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(7):2955-2962. doi: 10.1167/iovs.15-18505.
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Interleukin-37 is suggested as a novel proangiogenic factor in our previous study. In this study, the role of IL-37 was investigated in proliferative diabetic retinopathy (PDR).
Vitreous fluids from 10 patients with PDR and 8 controls were collected. The levels of IL-37 were determined by ELISA and the relationship between IL-37 and VEGF-A/Ang-2 was analyzed. The effects of IL-37 on chorioretinal endothelial cell (RF/6A) proliferation, migration, and tube formation were determined by BrdU incorporation assay, Boyden chamber assay, scratch-wound assay and tube formation assay.
The concentration of IL-37 in the PDR group was 95.09 ± 5.22 pg/mL and 34.91 ± 5.61 pg/mL in control group (P = 0.001). The level of IL-37 was highly related to the level of Ang-2 (P = 0.009, r = 0.772) and VEGF-A (P = 0.003, r = 0.827) in the PDR group, and VEGF expression in RF/6A cell was upregulated by IL-37 at low concentration. Interleukin-37 remarkably promoted RF/6A cell proliferation and migration. Interleukin-37 (1 ng/mL) remarkably stimulated tube formation with an increase of 85.3% for total tubule length and 74.1% for branching points compared with PBS control.
The level of IL-37 is elevated in vitreous fluids of patients with PDR and correlates with the level of VEGF-A and Ang-2. Interleukin-37 stimulates proangiogenic response of retinal endothelial cells in vitro, suggesting the involvement of IL-37 in the pathogenesis of PDR.
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