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S.Y. Kim, T. Hasegawa, C. Merges, R. Grebe, D.S. McLeod, M.A. Johnson, B.C. Hansen, G.A. Lutty; Expression of Intracellular Adhesion Molecule–1 (ICAM–1) and Tumor Necrosis Factor–Alpha (TNF–a) in Eyes of Spontaneous Type 2 Diabetic Monkeys . Invest. Ophthalmol. Vis. Sci. 2005;46(13):421.
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Purpose: Proinflammatory factors may play an important role in development and progression of diabetic retinopathy. TNF–α and VEGF are known to induce the surface expression of ICAM–1 on endothelial cells. Elevated expression of ICAM–1 can induce the adhesion of circulating leukocytes to the endothelium. Subsequently, leukocytes adherent to the endothelium may be a cause of endothelial cell injury, vaso–occlusion, and ultimately capillary dropout in diabetic retinopathy. This study was performed in postmortem monkey eyes to evaluate the relationship between proinflammatory factors (TNF–α, VEGF) and ICAM–1 in diabetic retinopathy. Methods: Cryopreserved eyes were studied from 6 spontaneous type 2 diabetic and 4 nondiabetic Rhesus monkeys. Immunohistochemistry with streptavidin alkaline phosphatase (Bhutto et al., IOVS. 2004;45:1544) was performed with mouse anti–human TNF–α (Novus, 1:100), mouse anti–human ICAM–1 (R6.5, ATCC#HB–9580, 1:600), and rabbit anti–human VEGF A (Ab2, Oncogene, 1:100). Immunoreactivity was graded by three independent observers using a previously published grading system (McLeod et al, A. J. Path. 1995;147:642) Results: In diabetic retinal and choroidal vasculatures, the expression of TNF–α was significantly upregulated: p=0.011 in larger retinal vessels; p=0.012 in retinal capillaries; p=0.003 in choriocapillaris; and p=0.002 in larger choroidal vessels. ICAM–1 was also upregulated in diabetic monkey in larger retinal vessels (p=0.048), in retinal capillaries (p=0.005), in choriocapillaris (p=0.001) and in larger choroidal vessels (p=0.013). VEGF expression was upregulated only in larger choroidal vessels of diabetic monkeys (p<0.001).<br /Conclusions: TNF–α and ICAM–1 were overexpressed in the retinal and choroidal vasculatures of spontaneous type 2 diabetic monkey compared to controls, while increased expression of VEGF was limited to larger choroidal vessels. This finding suggests overexpression of TNF–α and ICAM–1 may enhance leukocyte adhesion and consequently the incidence of endothelial injury and capillary obstruction resulting in retinal and choroidal microangiopathy in diabetics.
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