naloxone and Retinal-Diseases

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.. 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.. 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.. 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.

Topics: Animals; Astrocytes; Blotting, Western; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Lipopolysaccharides; Male; Microglia; Morphine; Naloxone; Narcotic Antagonists; Optic Disk; Rats; Rats, Inbred BN; Receptors, Opioid; Reperfusion Injury; Retina; Retinal Diseases; Time Factors; Tumor Necrosis Factor-alpha

To investigate the effects of morphine administered after reperfusion in a rabbit model of ischemic retinopathy.. The right eyes of 54 albino New Zealand rabbits were randomly allocated into nine treatment groups (n = 6 in each group). The eyes in saline-control group received 0.1 mL of phosphate-buffered saline solution intravitreally. In the ischemia-saline group, ischemia was induced by raising the intraocular pressure to 150 mmHg for 60 minutes. Then 0.1 mL of phosphate-buffered saline solution was administered intravitreally 5 minutes after reperfusion. The eyes in three ischemia-morphine groups (ischemia-morphine 0 hour, 1 hour, and 18 hours) received 0.1 mL of morphine (10 micromol/L) intravitreally 5 minutes, 1 hour, or 18 hours after termination of 60 minutes of ischemia, respectively. The eyes in ischemia-naloxone-morphine group received 0.05 mL of naloxone (10 micromol/L) intravitreally followed by injection of 0.05 mL morphine (10 micromol/L) 5 minutes after termination of ischemia. Toxicity controls were performed with morphine (10 micromol/L) and naloxone (10 micromol/L) without ischemia. Histologic evaluation was performed for all groups on the seventh postoperative day.. Sixty minutes of ischemia led to severe cell loss in ganglion cell layer and thinning of the inner nuclear layer in ischemia-saline group compared with that of the saline-control group (P < 0.001). Thickness of the inner plexiform layer to the inner limiting membrane (a measure of inner retinal thickness) was significantly increased due to edema (P < 0.001). Administration of morphine 5 minutes after reperfusion significantly improved all of the above mentioned indices compared with ischemia-saline group (P < 0.001). Administration of morphine 1 hour after reperfusion had also a significant effect on the improvement of above mentioned indices compared with saline-control group (P < 0.05). However, the number of ganglion cells was significantly higher in ischemia-morphine 0 hour group compared with ischemia-morphine 1 hour group (P < 0.001). Morphine treatment 18 hours after reperfusion did not change the amount of injury. Administration of naloxone 5 minutes before morphine abolished most of the morphine protective effects.. Intravitreal administration of morphine immediately after reperfusion maximally protects retina against ischemia-reperfusion injury. Pharmacologic evidence suggests that this protective phenomenon may be mediated in part by opioid receptors.

Topics: Analgesics, Opioid; Animals; Disease Models, Animal; Injections; Male; Morphine; Naloxone; Narcotic Antagonists; Rabbits; Reperfusion Injury; Retina; Retinal Diseases; Retinal Ganglion Cells; Time Factors; Vitreous Body