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Makiko Matsumoto, Kiyoshi Suzuma, Toshihide Maki, Hirofumi Kinoshita, Eiko Tsuiki, Azusa Fujikawa, Takashi Kitaoka; The Positive Feed Back Mechanism to Succinate by VEGF in Proliferative Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5938.
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Although vascular endothelial growth factor (VEGF) is a primary mediator of retinal angiogenesis, VEGF inhibition alone is insufficient to prevent retinal neovascularization. Hence, it is postulated that there are other potent ischemia-induced angiogenic factors. There is a report that succinate accumulates in the hypoxic retina of rodents and, via its cognate receptor G protein-coupled receptor-91 (GPR91), is a potent mediator of vessel growth in the settings of both normal retinal development and proliferative ischemic retinopathy. Last year, we reported the increase of succinate concentration in the vitreous body with proliferative diabetic retinopathy. In this report, we measured the succinate concentration in the vitreous body with proliferative diabetic retinopathy after intravitreal bevacizumab injection (IVB). We obtained a new result and report it.
We measured the level of succinate in the vitreous body of 85 eyes in 76 proliferative diabetic retinopathy (PDR) patients by selected ion monitoring mode of liquid chromatography-mass spectrometry. The 85 eyes were divided into three groups: active retinopathy without IVB group (APDR group, 21 eyes) ; quiescent retinopathy group (QPDR group, 24 eyes) ; active retinopathy with IVB group (IPDR group, 40 eyes). We measured VEGF and erythropoietin levels in the vitreous body with enzyme-linked immunosorbent assay.
The mean vitreous succinate levels were 3.42 µM in APDR group, 0.94 µM in QPDR group, and 1.17 µM in IPDR group. There were significant differences between APDR vs QPDR group (P< 0.01) and between APDR vs IPDR group (P< 0.01). The mean VEGF level in APDR group was also significantly higher than that in QPDR group and in IPDR group (1673, 102, n.d. pg/ml, respectively). The concentration of the erythropoietin, reported to increase in active PDR, was 2868mIU/ml in IPDR group > 733mIU/ml in APDR group > 319mIU/ml in QPDR group, respectively.
Although it is reported that succinate promotes expression of VEGF, the concentration of succinate decreased when VEGF was blocked. From this result, the succinate may be regulated by positive feed back mechanism of VEGF. Succinate and GPR91 receptor system may be a potential target to treat PDR.
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