title: α-Aminoadipic acid protects against retinal disruption through attenuating Müller cell gliosis in a rat model of acute ocular hypertension.
abstract: OBJECTIVE
  Ocular hypertension is an important risk factor for glaucoma. The purpose of this study was to investigate the gliotoxic effects of α-aminoadipic acid (AAA) in a rat model of AOH and its underlying mechanisms.
  
  
  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 transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) assay, and retinal ganglion cells (RGCs) immunostained with Thy-1 were counted. Müller cell activation was detected using immunostaining with glutamine synthetase and glial fibrillary acidic protein. Tumor necrosis factor-α (TNF-α) 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. Müller cell gliosis in the retinas of rats was induced, and retinal protein levels of TNF-α were increased. Intravitreal treatment of AAA versus PBS control attenuated these retinal abnormalities to show protective effects in the rat model of AOH.
  
  
  CONCLUSIONS
  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 of Müller cell gliosis and suppression of TNF-α induction. Our observations suggest that AAA might be a potential therapeutic target in glaucoma.
authors: Department of Ophthalmology, Beijing Friendship Hospital; Department of Neurobiology, Beijing Institute for Brain Disorders, Capital Medical University, Beijing.
authors: Xiaolei
authors: X
authors: Wang
authors: Department of Neurobiology, Beijing Institute for Brain Disorders, Capital Medical University, Beijing; Ningbo College of Health Sciences, Ningbo.
authors: Jier
authors: J
authors: Su
authors: Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing.
authors: Jingwen
authors: J
authors: Ding
authors: Department of Neurobiology, Beijing Institute for Brain Disorders, Capital Medical University, Beijing.
authors: Song
authors: S
authors: Han
authors: Department of Neurobiology, Beijing Institute for Brain Disorders, Capital Medical University, Beijing; Beijing Stomatological Hospital, Capital Medical University, Beijing, People's Republic of China.
authors: Wei
authors: W
authors: Ma
authors: Department of Neurobiology, Beijing Institute for Brain Disorders, Capital Medical University, Beijing.
authors: Hong
authors: H
authors: Luo
authors: University of California, Irvine School of Medicine, Irvine, CA, USA.
authors: Guy
authors: G
authors: Hughes
authors: Department of Ophthalmology, Beijing Friendship Hospital.
authors: Zhaoyang
authors: Z
authors: Meng
authors: Department of Ophthalmology, Beijing Friendship Hospital.
authors: Yi
authors: Y
authors: Yin
authors: Department of Ophthalmology, Beijing Friendship Hospital.
authors: Yanling
authors: Y
authors: Wang
authors: Department of Neurobiology, Beijing Institute for Brain Disorders, Capital Medical University, Beijing.
authors: Junfa
authors: J
authors: Li
mesh_terms: D015074:2-Aminoadipic Acid / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D063928:Ependymoglial Cells / Q000187:drug effects* / Q000473:pathology; D005911:Gliosis / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D015074:2-Aminoadipic Acid
keywords: Müller cells; TNF-α; acute ocular hypertension; glaucoma; retina; retinal ganglion cells; α-aminoadipic acid