title: Exenatide prevents high-glucose-induced damage of retinal ganglion cells through a mitochondrial mechanism.
abstract: Exenatide (exendin-4 analogue) is widely used in clinics and shows a neuroprotective effect. The main objectives of the present study were to prove that retinal ganglion cells (RGC-5) express GLP-1R, to ascertain whether exenatide prevents a high-glucose-induced RGC-5 impairment, to determine the appropriate concentration of exenatide to protect RGC-5 cells, and to explore the neuroprotective mechanisms of exenatide. Immunofluorescence and Western blot analyses demonstrated that RGC-5 cells express GLP-1R. We incubated RGC-5 cells with 25 mM glucose prior to incubation with either 25 mM glucose, 55 mM glucose (high), high glucose plus exenatide or high glucose plus a GLP-1R antagonist. The survival rates of the cells were measured by CCK-8, and cellular injury was detected by electron microscopy. There were statistical differences between the high-glucose group and the control group (P<0.05). Exenatide improved the survival rate of the cells and suppressed changes in the mitochondrial morphology. The optimum concentration of exenatide to protect the RGC-5 cells from high-glucose-induced RGC injury was 0.5 μg/ml, and this protective effect could be inhibited by exendin (9-39). To further study the mechanism underlying the beneficial effects of exenatide, the expression levels of cytochrome c, Bcl-2, Bax and caspase-3 were analysed by Western blot. The present study showed that treatment with exenatide significantly inhibited cytochrome c release and decreased the intracellular expression levels of Bax and caspase-3, whereas Bcl-2 was increased (P<0.05). These results suggested that GLP-1R activation can inhibit the cellular damage that is induced by high glucose. A mitochondrial mechanism might play a key role in the protective effect of exenatide on the RGC-5 cells, and exenatide might be beneficial for patients with diabetic retinopathy.
authors.affiliation: Department of Endocrinology, The First Clinical Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Hao
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Kuang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fu
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Gao
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
mesh_terms: D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D045304:Cytochromes c / Q000378:metabolism; D000077270:Exenatide; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000633:toxicity*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D014688:Venoms / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D003470:Culture Media; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D000077270:Exenatide; D053148:Caspase 3; D005947:Glucose