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Y. Bai, J.-X. Ma, Y.-Z. Le; The Role of Retinal Müller Cell-Produced VEGF in Ischemia Induced Vascular Leakage. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5899.
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Recent studies have shown that the overexpression of vascular endothelial growth factor (VEGF) is crucial for retinal neovascularization and vascular leakage, major pathological changes in diabetic retinopathy (DR). Retinal Müller cell is a major VEGF producer in the retina and is thought to be responsible for pathological changes in DR. To investigate the significance of Müller cell-produced VEGF in DR, we generated mice that had VEGF disruption in retinal Müller cells. The goal of this study is to determine the role of Müller cell-produced VEGF in ischemia-induced vascular leakage and its underline mechanism.
The conditional VEGF knockout mice were subjected to hypoxia using an oxygen-induced retinopathy (OIR) model. Retinal vascular leakage in the retina was determined by measurement of albumin leakage in the retina using immunohistochemistry (IHC) and Western-blot. Expression of occludin, a tight junction protein, in the retinal vessels was determined by IHC and Western-blot.
Loss of Müller cell-produced VEGF caused a reduction in ischemia-induced vascular leakage and prevented the decrease of occludin expression.
Our study suggests that the Müller cell-produced VEGF plays a crucial role in ischemia-induced vascular leakage through attenuation of tight-junction protein expression in retinal vessels.
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