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J. Wang, Y.-Z. Le; The Role of the Müller Cell-Produced VEGF in Inflammatory Response During the Pathogenesis of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5372.
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Diabetic retinopathy (DR) is considered as an inflammatory disease. Vascular endothelial growth factor (VEGF) is a proinflammatory factor that plays an essential role in the pathogenesis of DR. It has been suggested that retinal Müller cells are the major source of VEGF in DR. To dissect the function of the Müller cell-produced VEGF in inflammation, an early pathological change in DR, we determined the role of Müller cell-produced VEGF in inflammatory response using conditional VEGF knockout (KO) mice under diabetic stress.
The conditional VEGF KO mice were generated by mating of our Müller cell expressing Cre mice with the floxed VEGF mice. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ). Four weeks after the onset of diabetes, the retinal homogenates were used to evaluate the expression of inflammation markers, TNF- and ICAM-1, with Western blot. Leukostasis was determined by counting the number of fluorescein-labeled leukocytes inside the retinal vasculature.
The expression of ICAM-1 and TNF- was downregulated in the retina of diabetic conditional VEGF knockout mice. The number of adhesion leukocytes in the retinal vessels was also reduced.
Our results suggest that disruption of Müller cell-produced VEGF alone significantly attenuates retinal inflammation, an early pathological changes in DR. This information is potentially important for the therapeutics of DR, a leading cause of blindness.
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