TY - JOUR
T1 - Intravitreal injection of exendin-4 analogue protects retinal cells in early diabetic rats
AU - Zhang, Yu
AU - Zhang, Jingfa
AU - Wang, Qingping
AU - Lei, Xia
AU - Chu, Qing
AU - Xu, Guo Tong
AU - Ye, Wen
PY - 2011/1
Y1 - 2011/1
N2 - PURPOSE. To evaluate the protective effect of intravitreal injection of exendin-4 analogue (E4a) in early diabetic retinopathy (DR) and to explore its possible mechanism. METHODS. Forty Sprague-Dawley rats were divided into three groups: normal (N), diabetic (D), and E4a-treated diabetic rats (E4a). Diabetes was induced by streptozotocin. Rats in the E4a group were treated with E4a (0.1μg/2μL/eye), whereas the N and D groups were treated with the equivalent volume of normal saline. Electroretinography was performed at 1 month and 3 months after diabetes onset. Thicknesses and cell counts in each layer of the retina were evaluated. The concentration of glutamate was measured by high-performance liquid chromatography (HPLC). Expressions of glucagon-like peptide-1 receptor (GLP-1R) and GLAST (excitatory amino acid transporter) were detected at mRNA and protein levels and verified by immunohistochemistry in vitro and in vivo. The rMc-1 cells were cultured under high-glucose medium (25 mM), which mimicked diabetic conditions. Effects of E4a (10μg/mL) were also tested in the rMc-1 culture system. RESULTS. E4a prevented the reduction in b-wave amplitude and oscillatory potential amplitude caused by diabetes. It also prevented the cell loss of outer nuclear layer and inner nuclear layer; the thickness and cell count in the outer nuclear layer were decreased in 1-month diabetic rats. The concentration of glutamate in the retina was higher in diabetic rats and was significantly reduced in the E4a-treated group. Consistent with such changes, retinal GLP-1R and GLAST expression were reduced in the diabetic retina but upregulated in E4a-treated rats. No improvement was found in the retina in both functional and morphologic parameters 3 months after treatment.
AB - PURPOSE. To evaluate the protective effect of intravitreal injection of exendin-4 analogue (E4a) in early diabetic retinopathy (DR) and to explore its possible mechanism. METHODS. Forty Sprague-Dawley rats were divided into three groups: normal (N), diabetic (D), and E4a-treated diabetic rats (E4a). Diabetes was induced by streptozotocin. Rats in the E4a group were treated with E4a (0.1μg/2μL/eye), whereas the N and D groups were treated with the equivalent volume of normal saline. Electroretinography was performed at 1 month and 3 months after diabetes onset. Thicknesses and cell counts in each layer of the retina were evaluated. The concentration of glutamate was measured by high-performance liquid chromatography (HPLC). Expressions of glucagon-like peptide-1 receptor (GLP-1R) and GLAST (excitatory amino acid transporter) were detected at mRNA and protein levels and verified by immunohistochemistry in vitro and in vivo. The rMc-1 cells were cultured under high-glucose medium (25 mM), which mimicked diabetic conditions. Effects of E4a (10μg/mL) were also tested in the rMc-1 culture system. RESULTS. E4a prevented the reduction in b-wave amplitude and oscillatory potential amplitude caused by diabetes. It also prevented the cell loss of outer nuclear layer and inner nuclear layer; the thickness and cell count in the outer nuclear layer were decreased in 1-month diabetic rats. The concentration of glutamate in the retina was higher in diabetic rats and was significantly reduced in the E4a-treated group. Consistent with such changes, retinal GLP-1R and GLAST expression were reduced in the diabetic retina but upregulated in E4a-treated rats. No improvement was found in the retina in both functional and morphologic parameters 3 months after treatment.
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U2 - 10.1167/iovs.09-4727
DO - 10.1167/iovs.09-4727
M3 - Article
C2 - 20688733
AN - SCOPUS:79952230999
SN - 0146-0404
VL - 52
SP - 278
EP - 285
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 1
ER -