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A. Cacciamani, C. Stampley, A. Mammen, C. Senatore, F. Facchiano, M. Parravano, L. Di Renzo, M. Varano, M. Bartoli; Altered Expression Pattern of the CD47 Ligands, Thrombospondin-1 and Signal Regulated Proteins Alpha and Gamma, in Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5633.
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We have recently shown that the expression of the integrin activating protein CD47, a critical regulator of inflammatory and pro-thrombotic processes, is increased on circulating immunocytes of diabetic patients as well as in post-mortem retinas of diabetic donors. Here we further investigated the expression pattern of its ligands, thombospondin-1 (Tsp-1) and signal regulated proteins alpha and gamma (SIRP alpha and SIRP gamma, respectively).
Western analysis was conducted to determine levels of Tsp-1 in human post-mortem retinas and vitrei (obtained from Georgia Eye Bank) as well as levels of SIRPalpha and gamma. Flow cytometry analysis was conducted to assess levels of SIRPalpha and gamma in circulating immunocytes of Type 1 and Type 2 diabetic patients and healthy volunteers.
The expression pattern of SIRPalpha on circulating immunocytes of diabetic patients and in post-mortem human retinas of diabetic donors was diminished. In contrast, SIRPgamma protein levels were found augmented in these two tissues. Increased levels of Tsp-1 were found in sera of diabetic patients as well as in post-mortem vitreal and retinal specimens from diabetic donors.
Our data show that hyperglycemia modifies the expression pattern of CD47 and its ligands by favoring CD47 binding to the pro-inflammatory and the pro-thrombotic ligands,SIRPgamma and Tsp-1, respectively. These effects are associated with progression to DR, thus suggesting that altered CD47/SIRPalpha and gamma/Tsp-1 axis in involved in DR pathogenesis and its monitoring may hold diagnostic value.
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