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Xiaomeng Wang, Beiying Qiu, Lei Zhou, Ning Cheung, Gemmy Cheung, Tien Yin Wong, Wanjin Hong; The role of a novel regulator of Wnt signalling in ocular angiogenesis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5480.
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Abnormal blood vessel growth is a hallmark of many blinding eye diseases, including proliferative diabetic retinopathy (PDR). Proteomics analysis of patient vitreous samples revealed that the level of a novel regulator of Wnt signaling pathway, SIPRAD001, was significantly lower in vitreous of PDR patients compared to that in control patients. The purpose of this study is to investigate the functional role of SIPRAD001 in retinal vascular endothelial cell and angiogenesis
Western blot analysis was used to confirm the expression of SIPRAD001 in vitreous of PDR and control patients. Total RNA was extracted from mouse retinae and reverse transcribed into cDNA before being used for qRT-PCR to analyze the expression level of SIPRAD001 in mouse retinae. Immunofluorescence was performed to evaluate the expression pattern of SIPRAD001 in retinae subjected to oxygen-induced pathological neovascularization. Choroid sprouting assay, proliferation assay and tube formation assay were used to study the impact of SIPRAD001 on endothelial cell function and ocular angiogenesis.
Consistent with the proteomics study, our data showed a reduced SIPRAD001 level in vitreous of PDR patients as compared to that in control patients. Despite no change of SIPRAD001 expression level, immunofluorescence staining revealed that it is highly enriched in pathological vessels in retinae subjected to oxygen-induced retinopathy. We further demonstrated that recombinant SIPRAD001 inhibited vessel outgrowth from mouse choroid explants in a dose dependent manner. SIPRAD001 also significantly inhibited HRMEC proliferation and tube formation.
This study provided evidence that SIPRAD001 is strongly associated with pathological neovascularization in the eye and PRAD001 inhibited blood vessel formation in both ex vivo and in vitro models.
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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