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M. Bartoli, L. Di Renzo, E. Trifiro', A. Montemari, F. Lamoke, F. M. Pulcinelli, C. Parravano, D. M. Marcus, M. Varano; Increased Expression of the Integrin-interacting Protein, CD47, in Experimental and Human Diabetes: Implication in the Pathogenesis of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6168.
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Enhanced inflammatory and pro-thrombotic signals have been implicated in the pathogenesis of diabetic retinopathy (DR). The integrin-interacting protein, CD47, which is expressed on the surface of endothelial cells, immunocytes and platelets, has been recently shown to be a modulator of immune and pro-thrombotic signals and may be involved in vascular dysfunction. In the present study we wanted to determine the expression levels of CD47 in retinas of streptozotocin-induced diabetic rats (STZ-rats). In addition we examined the levels of CD47 on circulating monocytes of patients affected by Type 1 or Type 2 diabetes mellitus (T1DM and T2DM, respectively).
Western blotting analysis was conducted to asses the expression levels of CD47 in the retinas of STZ-rats, after 2 and 4 weeks of hyperglycemia in comparison to age-matched normoglycemic rats (ND). CD47 retinal localization was determined by immunohistochemical analysis. Patients, T1DM (n=14) and T2DM (n=23), were monitored for blood glucose and values of glycated hemoglobin. Circulating monocytes, isolated from T1DM and T2DM patients and from healthy age-matched controls (NDM, n=14), were stained with specific anti-CD47 antibodies and analyzed by flow cytometry. Fluorescein angiography was performed to assess clinical evidence of retinopathy following standard protocols.
Hyperglycemia enhanced the expression levels of CD47 in retinas of STZ-rats versus normoglycemic age-matched control. Immunohistochemistry revealed that CD47 localizes to microglia and around blood vessels. Monocytes, isolated from TD1M and T2DM patients exhibited higher (3 folds, p<0.05) CD47 expression in all the T1DM and T2DM patients versus NDM. In addition, CD47 expression appeared to be prominently increased in patients presenting clinical evidence of DR versus diabetic patients without DR.
The experimental and clinical evidence here presented shows that hyperglycemia stimulates the expression of CD47 in retinal microglia and circulating monocytes and it is positively correlated with progression of DR. These data are, therefore, suggesting a possible role for CD47 in the induction of diabetes-stimulated inflammatory and pro-thrombotic signals which may lead to DR.
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