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Sze Yuan Ho, Beiying Qiu, Gemmy Cheung, Tien Yin Wong, Wanjin Hong, Xiaomeng Wang; The role of a novel metabolic regulator in human retinal vascular endothelial cell function. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2642.
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© ARVO (1962-2015); The Authors (2016-present)
While anti-VEGF agents have revolutionized the treatment for ocular angiogenic diseases, including proliferative diabetic retinopathy, a substantial proportion of patients are resistant to the therapy. Emerging evidence suggested an intimate association between altered cell metabolism and neovascularization. Targeting cell metabolism may offer an alternative and more effective strategy to control excessive blood vessel formation. In this study, we aim to investigate the impact of SIPRAD007, a novel metabolic regulator with lipase property, on retinal vascular endothelial cell function.
MTS assay and Matrigel tube formation assay were performed using primary human retinal microvascular endothelial cells (HRMECs) to evaluate the role of SIPRAD007 in HRMEC function. The effect of SIPRAD007 on TNFα-induced expression of cell adhesion molecules, ICAM-1 and VCAM-1, was studied by real-time quantitative polymerase chain reaction (RT-qPCR). SIPRAD007’s role in TNFα-mediated monocyte adhesion was studied as described (Lowe & Raj, 2015).
Our study showed that the viability of SIPRAD007 siRNA transfected HRMECs was reduced by 18.9 ± 2.7% (n=3) as compared to scrambled siRNA treated HRMECs. SIPRAD007 silencing also inhibited HRMEC tube formation leading to 40.5 ± 12.5% (n=4) and 21.0 ± 4.2% (n=4) reduction on the number of junctions and total tube length respectively. In addition, SIPRAD007 silencing attenuated both TNFα-induced monocyte adhesion on the retinal endothelium and the expression of cell adhesion molecules, ICAM-1 and VCAM-1.
Our results demonstrated that a novel metabolic regulator, SIPRAD007, regulates both retinal endothelial cell function and TNFα-mediated inflammatory response.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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