March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Delta-Opioid Agonist Targets TNF-α and NF-B During Retinal Ischemic Injury
Author Affiliations & Notes
  • Shahid Husain
    Ophthalmology, Medical Univ of South Carolina, Charleston, South Carolina
  • Yasir Abdul
    Ophthalmology, Medical Univ of South Carolina, Charleston, South Carolina
  • Footnotes
    Commercial Relationships  Shahid Husain, None; Yasir Abdul, None
  • Footnotes
    Support  NIH (EY-019081)
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 5323. doi:
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      Shahid Husain, Yasir Abdul; Delta-Opioid Agonist Targets TNF-α and NF-B During Retinal Ischemic Injury. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5323.

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

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Abstract

Purpose: : To study the neuroprotective role of a Δ-opioid agonist, SNC-121, and determine potential targets in the optic nerve and retina for neuroprotection against retinal ischemic injury.

Methods: : Retinal ischemia was induced in Brown Norway rats by raising intraocular pressure (IOP) above systolic blood pressure (155-160mmHg) for 45 minutes. Rats 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 seven days following ischemic injury. Structural integrity of the retinal layers was determined by hematoxylin-eosin staining. Selected rats were treated with a Δ-opioid-receptor antagonist, naltrindole (3 mg/kg, i.p.), 15 minutes prior to the SNC-121 treatment. TNF-alpha and NF-ΚB were measured by immunohistochemistry and Western blot analyses.

Results: : In eyes subjected to 45 minutes of ischemia, mean b-wave amplitudes were significantly reduced when compared to the control eyes (control eyes 646±75 vs. ischemic eyes 321±59 μvolts; P<0.05), as determined by ERG measurement 7 days following retinal ischemia. In contrast, the b-wave amplitudes were significantly greater in the animals treated with SNC-121 for 7 days (ischemic eyes 321±59 vs. SNC-121 + ischemic eyes 508±50 μvolts, P<0.05). SNC-121-mediated retina neuroprotection was completely abolished when animals were treated with a highly selective Δ-opioid-receptor antagonist, naltrindole (3 mg/kg), 15 minutes prior to SNC-121 treatment (SNC-121 + ischemic eyes 508±50 vs. naltrindole + SNC-121 + ischemic eyes 348±57 μvolts; P<0.05). In addition, degeneration of the inner retina resulted in 36% reduction in overall retina thickness, and this reduction was almost fully recovered in SNC-121-treated animals. Pretreatment with naltrindole reversed the structural retina protection induced by SNC-121. There was a robust increase in TNF-α and NF-ΚB production in the optic nerve and inner retina layers 4-hours post-ischemia. The production of both TNF-α and NF-ΚB was attenuated in the presence of SNC-121.

Conclusions: : These results provide evidence that post-ischemia activation of Δ-opioid-receptors provides retina neuroprotection. Current data also demonstrate that production of TNF-α and NF-ΚB are early events in ischemic injury, which are opposed by Δ-opioid-receptor-activation. Overall, these results provide evidence that the Δ-opioidergic system exhibits the potential to protect the retina against ischemic injury.

Keywords: ischemia • neuroprotection • inflammation 
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