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Intravitreal injection of exendin-4 analogue protects retinal cells in early diabetic rats.
Invest Ophthalmol Vis Sci. 2011 Jan 05; 52(1):278-85.IO

Abstract

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 (0.1 μg/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 (10 μg/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.

CONCLUSIONS

Intravitreal administration of E4a can prevent the retina, functionally and morphologically, from the insults of diabetes in rats. GLP-1R and GLAST were proved to exist in the rat retina, and their lowered expressions in the diabetic retina might be related to retinal damage by increasing the retinal glutamate. E4a might protect the retina by reducing the glutamate level through upregulating GLP-1R and GLAST, as observed in retinal Müller cells in this study, but this protective effect was transient. Thus, this could be a potential approach for the treatment of DR.

Authors+Show Affiliations

Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20688733

Citation

Zhang, Yu, et al. "Intravitreal Injection of Exendin-4 Analogue Protects Retinal Cells in Early Diabetic Rats." Investigative Ophthalmology & Visual Science, vol. 52, no. 1, 2011, pp. 278-85.
Zhang Y, Zhang J, Wang Q, et al. Intravitreal injection of exendin-4 analogue protects retinal cells in early diabetic rats. Invest Ophthalmol Vis Sci. 2011;52(1):278-85.
Zhang, Y., Zhang, J., Wang, Q., Lei, X., Chu, Q., Xu, G. T., & Ye, W. (2011). Intravitreal injection of exendin-4 analogue protects retinal cells in early diabetic rats. Investigative Ophthalmology & Visual Science, 52(1), 278-85. https://doi.org/10.1167/iovs.09-4727
Zhang Y, et al. Intravitreal Injection of Exendin-4 Analogue Protects Retinal Cells in Early Diabetic Rats. Invest Ophthalmol Vis Sci. 2011 Jan 5;52(1):278-85. PubMed PMID: 20688733.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2011/01/05/ PY - 2010/8/7/entrez PY - 2010/8/7/pubmed PY - 2011/2/8/medline SP - 278 EP - 85 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 52 IS - 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 (0.1 μg/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 (10 μg/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. CONCLUSIONS: Intravitreal administration of E4a can prevent the retina, functionally and morphologically, from the insults of diabetes in rats. GLP-1R and GLAST were proved to exist in the rat retina, and their lowered expressions in the diabetic retina might be related to retinal damage by increasing the retinal glutamate. E4a might protect the retina by reducing the glutamate level through upregulating GLP-1R and GLAST, as observed in retinal Müller cells in this study, but this protective effect was transient. Thus, this could be a potential approach for the treatment of DR. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/20688733/Intravitreal_injection_of_exendin_4_analogue_protects_retinal_cells_in_early_diabetic_rats_ L2 - http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.09-4727 DB - PRIME DP - Unbound Medicine ER -