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Abstract #46614 Published in IGR 13-3
Opioid receptor activation: Suppression of ischemia/reperfusion-induced production of TNF-(alpha) in the retina
Husain S; Liou GI; Crosson CEInvestigative Ophthalmology and Visual Science 2011; 52: 2577-2583
PURPOSE. The detrimental role of TNF-(alpha) in ischemia-induced tissue damage is known. The authors study examined whether opioid receptor activation alters TNF-(alpha) 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 (mu)M) for 24 hours and then treated with 10 (mu)g/mL or 30 ng/mL lipopolysaccharide (LPS), respectively. TNF-(alpha) 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-(alpha) production; the maximum production occurred at 4 hours after ischemia and localized to the inner retinal regions. Ischemiainduced TNF-(alpha) production was significantly inhibited by morphine. In astrocytes and microglia, LPS triggered a robust increase in the release of TNF-(alpha), which was significantly inhibited (P < 0.05) by morphine. Naloxone reversed the morphineinduced suppression of TNF-(alpha) production in vivo and in vitro. Both ONH astrocytes and microglial cells expressed (delta)-, (kappa)-, and (mu)-opioid receptor subtypes. CONCLUSIONS. These data provide evidence that the production of TNF-(alpha) after ischemia/reperfusion injury is an early event and that opioid receptor activation reduces the production of TNF-(alpha). Immunohistochemistry data and in vitro studies provide evidence that ONH astrocytes and microglial cells are the primary sources for the TNF-(alpha) production under ischemic/inflammatory conditions. Activation of one or more opioid receptors can reduce ischemic/reperfusion injury by the suppression of TNF-(alpha) production.
S. Husain. Hewitt Laboratory, Ola B. Williams Glaucoma Center, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, 167 Ashley Avenue, Charleston, SC 29425, United States.
Classification:
5.3 Other (Part of: 5 Experimental glaucoma; animal models)
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.3 Immunohistochemistry (Part of: 3 Laboratory methods)
