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X. Yu, L. Ping; The Study on the Contineous Expression of Glutamine Synthetase in Retina of Chronic Diabetic Rats. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3609.
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The long term and insidious characteristics of diabetic retina(DR) require a time-dependent biomarker that allows evaluation of disease progression and pathogenesis.To screen the potent clinical biomarkers in the chronic diabetic retina(DR),total transcriptome of diabetic retina of rats were studied and optimal individual candidate was furtherly evaluated in time-dependent duration.
Series Analysis of Gene Expression (SAGE) technology was used to the initial screen to find optimal biomarkers using streptozotocin-induced diabetic rats .Glutamine synthetase (GS) as the maxium varible candidate protein was selected and furtherly measured in the rat retina at various time points after diabetes induction.Northern blot,RT-PCR and colorimetric enzyme activity assays were synchronously used to compare the differences between diabetic retinopathical rats and healthy controls.GS mRNA expression and enzyme activity comparison were followed up over a 12-month period.
RT-PCR and colorimetric enzyme activity assays revealed significant differences in GS mRNA expression and enzyme activity as early as the first month of diabetes development, with a progressive decrease in GS mRNA level and enzyme activity over a 12-month period. Northern blot analysis indicated a linear correlation between the reduction in GS expression and the time course of diabetic retinopathy (r=0.802, p<0.0001), which was validated by real-time RT-PCR (r=0.731, p<0.001).
Our results implicate GS as a potential biomarker for evaluating the severity of diabetic retinopathy over the time course of diabetes progression.
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