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S. Husain, D. E. Potter, C. E. Crosson; Opioid Receptor Activation Is Required for the Development of Retinal Ischemic Preconditioning. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4198.
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Studies have shown that retinal ischemic preconditioning (IPC) can protect retina from subsequent ischemic injury. Current studies were designed to test the hypothesis that opioid receptor activation is required for the development of retinal ischemic preconditioning.
Ischemic preconditioning was induced in anesthetized female Brown Norway rats by raising intraocular pressure (IOP) above systolic blood pressure (155-160 mmHg) for 5 minutes. Rats were allowed to recover for 24 hours and subjected to a second 45 minutes period of ischemia. The contralateral eye was left untreated for the control. Selected rats were treated (i.p) with an opioid receptor antagonist, naloxone (3 mg/kg), for 1 hour prior to IPC event. In another group, rats were treated with morphine (0.1-10 mg/kg) 24 hours prior to the 45 minutes ischemic insult. To quantitate post-ischemic functional recovery, we performed electroretinograms seven days following 45 minutes ischemic insult. To asses the expressions of retinal opioid receptors, rats were euthanized, eyes enucleated, and fixed in 4% paraformaldehyde overnight. Retinal tissues were embedded in paraffin sections and stained with anti-Κ-opioid, anti-Δ-opioid, or anti-µ-opioid receptor antibodies.
After 45 minutes ischemia in rats resulted in a 50% reduction in b-wave amplitude seven days after the ischemic insult. Ischemic preconditioning (IPC) of the retina resulted in a significant improvement in b-wave amplitude. This IPC-induced protection was completely inhibited in the presence of opioid receptor antagonist, naloxone (3 mg/kg). In addition, administration of opioid receptor agonist, morphine, alone at the doses of 1 and 10 mg/kg prevented ischemic-induced reduction in b-wave amplitude significantly. Immunohistochemistry demonstrated that Κ-opioid, Δ-opioid, and µ-opioid receptors are expressed in the retinal areas; however, an intense staining was observed in the inner retinal layers.
These results provide evidence that opioid receptor activation plays a central role in the development of ischemic preconditioning. Furthermore, opioid receptor activation can mimic the ischemic preconditioning effects. Retinal ischemia plays a pivotal role in a number of retinal degenerative diseases such as glaucoma and diabetic retinopathy. Understanding the cellular mechanisms associated with retinal degeneration would be valuable in identifying new treatments for such blinding diseases.
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