title: Cannabidiol protects retinal neurons by preserving glutamine synthetase activity in diabetes.
abstract: OBJECTIVE
  We have previously shown that non-psychotropic cannabidiol (CBD) protects retinal neurons in diabetic rats by inhibiting reactive oxygen species and blocking tyrosine nitration. Tyrosine nitration may inhibit glutamine synthetase (GS), causing glutamate accumulation and leading to further neuronal cell death. We propose to test the hypothesis that diabetes-induced glutamate accumulation in the retina is associated with tyrosine nitration of GS and that CBD treatment inhibits this process.
  
  
  METHODS
  Sprague Dawley rats were made diabetic by streptozotocin injection and received either vehicle or CBD (10 mg/kg/2 days). After eight weeks, retinal cell death, Müller cell activation, GS tyrosine nitration, and GS activity were determined.
  
  
  RESULTS
  Diabetes causes significant increases in retinal oxidative and nitrative stress compared with controls. These effects were associated with Müller cell activation and dysfunction as well as with impaired GS activity and tyrosine nitration of GS. Cannabidiol treatment reversed these effects. Retinal neuronal death was indicated by numerous terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL)-labeled cells in diabetic rats compared with untreated controls or CBD-treated rats.
  
  
  CONCLUSIONS
  These results suggest that diabetes-induced tyrosine nitration impairs GS activity and that CBD preserves GS activity and retinal neurons by blocking tyrosine nitration.
authors.affiliation: Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA 30912, USA. aelremessy@mcg.edu
authors.forename: A B
authors.initials: AB
authors.lastname: El-Remessy
authors.forename: Y
authors.initials: Y
authors.lastname: Khalifa
authors.forename: S
authors.initials: S
authors.lastname: Ola
authors.forename: A S
authors.initials: AS
authors.lastname: Ibrahim
authors.forename: G I
authors.initials: GI
authors.lastname: Liou
mesh_terms: D000818:Animals; D002185:Cannabidiol / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015538:Nitrosation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D055351:Retinal Neurons / Q000201:enzymology* / Q000473:pathology*
chemical_list: D018696:Neuroprotective Agents; D002185:Cannabidiol; D053148:Caspase 3; D005974:Glutamate-Ammonia Ligase
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