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M. Rojas, W. Zhang, D. T. Nguyen, G. I. Liou, R. W. Caldwell, R. B. Caldwell; Diabetes-induced Retinal Vascular Inflammation Is Mediated by IL-6. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6166.
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The concentration of interleukin-6 (IL-6) has been found to be increased in vitreous samples from patients with diabetic retinopathy (DR), but the specific role of IL-6 in DR has not been determined. We have demonstrated previously that IL-6 mediates angiotensin II-induced retinal vascular inflammation. We have now extended this work to evaluate the participation of IL-6 in retinal inflammation in a mouse model of type I diabetes.
Wild type C57BL6 (WT) and IL-6 deficient mice (IL-6ko) were injected intraperitoneally with streptozotozin (75 mgr/kg) to induce diabetes. WT mice were used as controls. After 2 weeks of hyperglycemia, the mice were sacrificed and retinas were prepared for analysis of IL-6 mRNA by quantitative RT-PCR and for IL-6 localization as determined by immunohistochemistry with a specific antibody for IL-6. Vascular inflammation was determined by using an assay for leukostasis. Mice were anesthetized, perfused with Concanavalin A and the number of adherent leukocytes was counted.
Expression of IL-6 mRNA in the retina was increased by 55% as determined by quantitative PCR. Immunolocalization studies revealed strong IL-6 immunoreactivity in the inner plexiform layer and outer nuclear layer in retinal sections from diabetic mice but not in control mice. To address the role of IL-6 in diabetes-induced vascular inflammation, leukostasis was determined in WT and IL-6ko mice. Diabetes induced a dramatic increase in the number of leukocytes adherent to the retinal vessels. This increase was dramatically reduced in the IL-6ko mice (98 ± 8 vs 250 ± 46, P=<0.002).
Diabetes increases IL-6 expression within the retina. Lack of IL-6 blocks the action of diabetes in inducing retinal leukocyte adhesion to the retinal vessels. This result indicates that IL-6 is critically involved in retinal vascular inflammation during diabetic retinopathy.
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