Negative regulation of glucose transport alleviates microvasculature pathological changes of retinopathy in diabetic mice

Objective To investigate the effect of glucose transporter-1(GLUT1)suppression on microvasculature pathological changes in diabetic mice.Methods Thirty-six 8-week-old C57BL/6 mice were randomly divided into normal control,diabetic control and GLUT1 siRNA treatment groups.Diabetic model was established by intraperitoneal injection of streptozotocin.GLUT1 siRNA treatment group received intravitreal injection of siRNA-mediated GLUT1,and the other two groups received equal amount of non-specific siRNA.Twenty-one weeks after diabetic induction,immunoblotting was conducted to examine the expression of GLUT1 and two inflammation factors:ICAM-1and TNF-α.We also calculated the retinal glucose concentration.Leukostasis assay and vascular leakage assay were utilized to compare the microvasculature pathological changes between the two groups.Results The expression of GLUT1 was significantly down-regulated in GLUT1 siRNA treatment group compared with the other two groups(P0.01),decreased by 77.00%compared with the normal control group and only being 8.07% of the diabetic control group.Though retinal glucose concentration of diabetic control and GLUT1 siRNA treatment groups were higher than that of normal control,that in GLUT1 siRNA treatment group was only 50.05%that of the diabetic control group(P0.01).The expressions of ICAM-1and TNF-αin GLUT1 siRNA treatment and diabetic control were significantly higher than that in the normal control group,and their expressions in GLUT1 siRNA treatment group were 66.14%(P0.05)and 54.76%(P 0.01)those of the diabetic control group,respectively.Moreover,compared with GLUT1 siRNA treatment group,diabetic control group had more adherent leukocytes in the retinal microvasculature and larger areas of leaked FITC-labeled albumin retina.Conclusion GLUT1 siRNA can limit glucose transport into the retina by inhibiting GLUT1 expression,thus decrease retinal glucose concentration and alleviate microvasculature changes of diabetic retinopathy.