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Y. Zhang, J. Zhang, Q. Wang, X. Lei, G.-T. Xu, W. Ye; Intravitreal Injection of Exendin-4 Analogue Protects Retinal Cells in Early Experimental Diabetes. Invest. Ophthalmol. Vis. Sci. 2009;50(13):108.
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To explore and to evaluate the protective effect of exendin-4 analogue (E4a) on retinal cells of diabetic rats, after E4a was injected intravitreally at the onset of diabetes.
Expression of GLP-1R and GLAST were detected at both mRNA and protein levels and verified by immunohistochemistry in vitro and vivo. 36 SD rats were included in the experiment. Diabetes was induced by intraperitoneal injection (ip) of streptozotocin(STZ). The rats were divided into 3 groups: normal control (N), diabetic control (D) and E4a-treated diabetic (E4a) group. For E4a group, the rats were treated with E4a ; for N and D groups, the rats were treated with normal saline (NS, sc). Blood glucose levels and body weight were measured weekly. Electroretinogram (ERG) was performed 1 and 3 months after diabetes onset. The retinal thickness and cell counts in each layer were evaluated under light microscopy after ERG examination. The concentration of glutamate in retina was measured by HPLC.
GLP-1R and GLAST were expressed at both mRNA and protein levels in rat retina. Immunostaining of the rat retina revealed that GLP-1R was predominantly expressed in inner layer of the retina. GLAST was expressed in Muller cells and RGCs. B-wave amplitudes and OPs decreased with the progress of diabetes, and E4a prevents the loss of b-wave amplitude and OPs caused by diabetic rats. The retinal thickness was reduced with a diabetes-duration dependent fashion. The cell counts of both ONL and INL were reduced in the diabetic rats. E4a prevented the cell loss and maintained a normal thickness. The concentration of glutamate in E4a group was significantly reduced compared with the diabetic control. The protein level of GLAST in E4a group expressed more than diabetic control.
GLP-1R and GLAST are expressed in rat retina. Apoptosis is an important constituent of retinal cell death in early DR. E4a administration can reverse the changes of ERG, prevent the retinal cell death and maintain normal retinal thickness in diabetic rats. It can reduce the concentration of glutamate in retina through upregulating the expression of GLAST. Therefore, this is a potent approach for treatment of early DR.
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