title: Opioid receptor activation: suppression of ischemia/reperfusion-induced production of TNF-α in the retina.
abstract: OBJECTIVE
  The detrimental role of TNF-α in ischemia-induced tissue damage is known. The authors study examined whether opioid receptor activation alters TNF-α levels in the postischemic retina.
  
  
  METHODS
  Retinal ischemia was induced by raising the intraocular pressure above systolic blood pressure (155-160 mm Hg) for 45 minutes. Rats were pretreated with the opioid receptor agonist morphine (1 mg/kg; intraperitoneally) before injury. Selected animals were pretreated with the opioid antagonist naloxone (3 mg/kg; intraperitoneally). Human optic nerve head (ONH) astrocytes and rat microglial cells were treated with morphine (0.1-1 μM) for 24 hours and then treated with 10 μg/mL or 30 ng/mL lipopolysaccharide (LPS), respectively. TNF-α was measured by ELISA. Opioid receptor subtypes in astrocytes and microglia were determined by Western blot analysis.
  
  
  RESULTS
  There was a time-dependent increase in TNF-α production; the maximum production occurred at 4 hours after ischemia and localized to the inner retinal regions. Ischemia-induced TNF-α production was significantly inhibited by morphine. In astrocytes and microglia, LPS triggered a robust increase in the release of TNF-α, which was significantly inhibited (P < 0.05) by morphine. Naloxone reversed the morphine-induced suppression of TNF-α production in vivo and in vitro. Both ONH astrocytes and microglial cells expressed δ-, κ-, and μ-opioid receptor subtypes.
  
  
  CONCLUSIONS
  These data provide evidence that the production of TNF-α after ischemia/reperfusion injury is an early event and that opioid receptor activation reduces the production of TNF-α. Immunohistochemistry data and in vitro studies provide evidence that ONH astrocytes and microglial cells are the primary sources for the TNF-α production under ischemic/inflammatory conditions. Activation of one or more opioid receptors can reduce ischemic/reperfusion injury by the suppression of TNF-α production.
authors.affiliation: Hewitt Laboratory, Ola B. Williams Glaucoma Center, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, 167 Ashley Avenue, Charleston, SC 29425, USA. husain@musc.edu
authors.forename: Shahid
authors.initials: S
authors.lastname: Husain
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Liou
authors.forename: Craig E
authors.initials: CE
authors.lastname: Crosson
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D009898:Optic Disk / Q000166:cytology; D051381:Rats; D011914:Rats, Inbred BN; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D012164:Retinal Diseases / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D014409:Tumor Necrosis Factor-alpha; D009270:Naloxone; D009020:Morphine