机构：[1]Department of Ophthalmology, Beijing Friendship Hospital首都医科大学附属北京友谊医院[2]Department of Neurobiology, Beijing Institute for Brain Disorders, Capital Medical University, Beijing[3]Ningbo College of Health Sciences, Ningbo[4]Department of Ophthalmology,Beijing Tongren Hospital,Capital Medical University,Beijing首都医科大学附属北京同仁医院临床科室眼科眼整形科眼科(未分亚科)[5]Beijing Stomatological Hospital, Capital Medical University, Beijing, People’s Republic of China[6]University of California, Irvine School of Medicine, Irvine, CACA, USA
Objective: Ocular hypertension is an important risk factor for glaucoma. The purpose of this study was to investigate the gliotoxic effects of alpha-aminoadipic acid (AAA) in a rat model of AOH and its underlying mechanisms. Materials and methods: In the rat model of acute ocular hypertension (AOH), intraocular pressure was increased to 110 mmHg for 60 minutes. Animals were divided into four groups: sham operation (Ctrl), AOH, AOH + phosphate-buffered saline (PBS), and AOH + AAA. Cell apoptosis in the ganglion cell layer was detected with the terminal deoxynucleotidyl transferasemediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) assay, and retinal ganglion cells (RGCs) immunostained with Thy-1 were counted. Muller cell activation was detected using immunostaining with glutamine synthetase and glial fibrillary acidic protein. Tumor necrosis factor-alpha (TNF-alpha) was examined using Western blot. Results: In the rat model of AOH, cell apoptosis was induced in the ganglion cell layer and the number of RGCs was decreased. Muller cell gliosis in the retinas of rats was induced, and retinal protein levels of TNF-alpha were increased. Intravitreal treatment of AAA versus PBS control attenuated these retinal abnormalities to show protective effects in the rat model of AOH. Conclusion: In the retinas of the rat model of AOH, AAA treatment attenuated retinal apoptosis in the ganglion cell layer and preserved the number of RGCs, likely through the attenuation Muller cell gliosis and suppression of TNF-alpha induction. Our observations suggest that AAA might be a potential therapeutic target in glaucoma.
基金：
Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [XM201305]; Clinical-Basic Cooperation Program from Capital Medical University [14JL32, 2015YKSJ02]
第一作者机构：[1]Department of Ophthalmology, Beijing Friendship Hospital[2]Department of Neurobiology, Beijing Institute for Brain Disorders, Capital Medical University, Beijing
共同第一作者：
通讯作者：
通讯机构：[1]Department of Ophthalmology, Beijing Friendship Hospital[2]Department of Neurobiology, Beijing Institute for Brain Disorders, Capital Medical University, Beijing[*1]Department of Neurobiology, Beijing Institute for Brain Disorders, Capital Medical University, 10 Waixitoutiao, Youanmen, Fengtai District, Beijing 100069, People’s Republic of China[*2]Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, 95 Yong’an Road, Xicheng District, Beijing 100050, People’s Republic of China
推荐引用方式(GB/T 7714)：
Wang Xiaolei,Su Jier,Ding Jingwen,et al.alpha-Aminoadipic acid protects against retinal disruption through attenuating Muller cell gliosis in a rat model of acute ocular hypertension[J].DRUG DESIGN DEVELOPMENT AND THERAPY.2016,10:3449-3457.doi:10.2147/DDDT.S105362.
APA：
Wang, Xiaolei,Su, Jier,Ding, Jingwen,Han, Song,Ma, Wei...&Li, Junfa.(2016).alpha-Aminoadipic acid protects against retinal disruption through attenuating Muller cell gliosis in a rat model of acute ocular hypertension.DRUG DESIGN DEVELOPMENT AND THERAPY,10,
MLA：
Wang, Xiaolei,et al."alpha-Aminoadipic acid protects against retinal disruption through attenuating Muller cell gliosis in a rat model of acute ocular hypertension".DRUG DESIGN DEVELOPMENT AND THERAPY 10.(2016):3449-3457
