April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Role of -Opioid-Receptor Activation in Retina Neuroprotection Against Ischemic Retinal Injury
Author Affiliations & Notes
  • Yasir Abdul
    Ophthalmology, Medical University of South Carolina, Charleston, South Carolina
  • Craig E. Crosson
    Ophthalmology, Medical University of South Carolina, Charleston, South Carolina
  • Shahid Husain
    Ophthalmology, Medical University of South Carolina, Charleston, South Carolina
  • Footnotes
    Commercial Relationships  Yasir Abdul, None; Craig E. Crosson, None; Shahid Husain, None
  • Footnotes
    Support  EY019081
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2656. doi:
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      Yasir Abdul, Craig E. Crosson, Shahid Husain; Role of -Opioid-Receptor Activation in Retina Neuroprotection Against Ischemic Retinal Injury. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2656.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To determine the role of Δ-opioid-receptor activation in retina neuroprotection against ischemic retinal injury using endogenous and exogenous neuroprotective strategies.

Methods: : Brown Norway rats were used for ischemic preconditioning (IPC) and ischemia by raising intraocular pressure (IOP) above systolic blood pressure (155-160 mmHg) for 5 and 45 minutes, respectively. Selected rats were treated with a Δ-opioid-receptor antagonist (naltrindole, 3 mg/kg, i.p.) 1 hour prior to the IPC. Additionally, animals were treated with the Δ-opioid-receptor agonist SNC-121 (0.1-1 mg/kg; i.p.) 30 minutes post ischemia and daily, up to 7 days. To quantitate post-ischemic functional recovery, electroretinograms (ERG) were performed 7 days following ischemic injury. TNF-α and matrix metalloproteinase-2 (MMP-2) were measured by immunohistochemistry and Western blotting.

Results: : In eyes subjected to 45 minutes of ischemia, mean b-wave amplitudes were significantly reduced when compared to the contralateral control eyes (control 657 ±31 vs. ischemic eyes 343 ±33; P<0.05), as determined by ERG measurement 7 days following retinal ischemia. In eyes that received an ischemic preconditioning (IPC) stimulus 24-hours prior to the ischemic injury, the b-wave amplitudes were significantly greater in amplitude (P<0.05) when compared to the ischemic eyes. In contrast, IPC-mediated retina neuroprotection was completely abolished when animals were treated with a highly selective Δ-opioid-receptor antagonist, naltrindole (3 mg/kg), one hour prior to IPC (IPC + ischemic eyes 607±35 vs. naltrindole + IPC + ischemic eyes 197±35). Post-ischemia treatment of animals with SNC-121 (0.1-1 mg/kg; i.p.) for 7 days resulted in improvement in the b-wave amplitudes. There was a robust increase in TNF-α and MMP-2 production in the optic nerve head and inner retinal layers at 4-hours post ischemia. The production of both TNF-α and MMP-2 was attenuated in the presence of the opioid-receptor agonist.

Conclusions: : These results provide evidence that the endogenous activity of the Δ-opioid-receptor is required for IPC-mediated retina neuroprotection. In addition, exogenous activation of the Δ-opioid-receptor by SNC-121 provides retina neuroprotection against ischemic injury. Current data also demonstrate that production of MMP-2 and TNF-α are early events in ischemic injury, which are opposed by opioid-receptor-activation. Overall, these results provide evidence that the opioidergic system exhibits the potential to protect the retina against ischemic injuries.

Keywords: ischemia • neuroprotection • retina 
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