Time-dependent reduction of glutamine synthetase in retina of diabetic rats.
Diabetic Retinopathy (DR) is one of the most common complications of diabetes and a major cause of blindness worldwide. We studied the transcriptome of the diabetic retina using Series Analysis of Gene Expression (SAGE) technology and observed a 45.6% reduction in transcript levels of glutamine synthetase (GS) in streptozotocin-induced diabetic rats compared with normal rats. 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 possible biomarker for evaluating the severity of developed diabetic retinopathy over the time course of diabetes progression.
Yu
Xu-hui
XH
Department of Ophthalmology, The First Hospital of Harbin Medical University, Harbin 150001, China.
Zhang
Hong
H
Wang
Yu-hong
YH
Liu
Li-juan
LJ
Teng
Yan
Y
Liu
Ping
P
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015152:Blotting, Northern; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000235:genetics; D003930:Diabetic Retinopathy / Q000201:enzymology* / Q000235:genetics; D018450:Disease Progression; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D015723:Gene Library; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000201:enzymology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D015415:Biomarkers; D012333:RNA, Messenger; D005974:Glutamate-Ammonia Ligase