title: The glucagon like peptide 1 analogue, exendin-4, attenuates oxidative stress-induced retinal cell death in early diabetic rats through promoting Sirt1 and Sirt3 expression.
abstract: This study was aimed to further investigate the possible mechanisms by which the glucagon like peptide 1 analogue, exendin-4 (EX4), protects rat retinal cells at the early stage of diabetes. EX4 was injected intravitreally into normal and early-stage streptozotocin-diabetic rats. Cell death, reactive oxygen species (ROS), and electroretinogram (ERG) were measured. Sirtuin (Sirt) mRNA and protein were analyzed. In retinas of diabetic rats 1 month after diabetes onset, cell death and ROS level increased significantly, and the b-wave amplitudes and OPs were significantly reduced. Four days after intravitreal EX4 treatment, retinal cell death and ROS level in retinas reduced significantly, and visual function was recovered. In the retinas of early-stage diabetic rats, the expressions of Sirt1 and Sirt3 were also found to be significantly decreased, and both were back to normal levels after intravitreal injection of EX4. In R28 cells, hydrogen peroxide (H2O2) treatment increased ROS and cell death and decreased Sirt1 and Sirt3. With the addition of EX4 into the culture system, the expressions of Sirt1 and Sirt3 were increased, and the H2O2-induced ROS and cell death were significantly reduced. These results confirm a mechanism for EX4 to protect retinal cells from diabetic damage and oxidative injury. EX4 reduces retinal cell death and ROS generation by upregulating Sirt1 and Sirt3 expressions in the retina of early-stage diabetic rats as well as in H2O2-treated R28 cells.
authors.affiliation: Department of Ophthalmology of the Shanghai Tenth People's Hospital, and Laboratory of Clinical Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, China; Institute of Cardiovascular Disease, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology of the Shanghai Tenth People's Hospital, and Laboratory of Clinical Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology of the Shanghai Tenth People's Hospital, and Laboratory of Clinical Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology of the Shanghai Tenth People's Hospital, and Laboratory of Clinical Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Ophthalmology of the Shanghai Tenth People's Hospital, and Laboratory of Clinical Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Ophthalmology of the Shanghai Tenth People's Hospital, and Laboratory of Clinical Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Shijia
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology of the Shanghai Tenth People's Hospital, and Laboratory of Clinical Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Shuqing
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Ophthalmology of the Shanghai Tenth People's Hospital, and Laboratory of Clinical Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Jingfa
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology of the Shanghai Tenth People's Hospital, and Laboratory of Clinical Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Drexel University College of Medicine, Media, PA, USA.
authors.forename: Weiye
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Ophthalmology of the Shanghai Tenth People's Hospital, and Laboratory of Clinical Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China. Electronic address: lulixia@tongji.edu.cn.
authors.forename: Lixia
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Ophthalmology of the Shanghai Tenth People's Hospital, and Laboratory of Clinical Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai, China; Institute for Nutritional Sciences, Tongji University, Shanghai, China. Electronic address: xuguotong@tongji.edu.cn.
authors.forename: Guo-Tong
authors.initials: GT
authors.lastname: Xu
mesh_terms: D000818:Animals; D016923:Cell Death; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004596:Electroretinography; D000077270:Exenatide; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D056564:Sirtuin 1 / Q000096:biosynthesis / Q000235:genetics*; D037761:Sirtuins / Q000096:biosynthesis / Q000235:genetics*; D013997:Time Factors; D014688:Venoms / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D010455:Peptides; D012333:RNA, Messenger; C000607791:SIRT3 protein, rat; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D037761:Sirtuins
keywords: Cell death; Diabetic retinopathy; Exendin-4; Oxidative stress; Sirtuin