June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Novel Targets of Delta Opioid-Receptor for RGC Neuroprotection
Author Affiliations & Notes
  • Shahid Husain
    Ophthalmology, Medical University of South Carolina, Charleston, SC
  • Anis Ahmad
    Ophthalmology, Medical University of South Carolina, Charleston, SC
  • sudha Singh
    Ophthalmology, Medical University of South Carolina, Charleston, SC
  • Footnotes
    Commercial Relationships Shahid Husain, None; Anis Ahmad, None; sudha Singh, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2481. doi:
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      Shahid Husain, Anis Ahmad, sudha Singh; Novel Targets of Delta Opioid-Receptor for RGC Neuroprotection. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2481.

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

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Purpose: This study was designed to identify the downstream targets of delta opioid-receptors for RGC neuroprotection during glaucomatous injury.

Methods: Brown Norway rats were used to elevate intraocular pressure (IOP) by injecting 50 µL of 2M hypertonic saline into the circumferential limbal veins. IOP was recorded as the average of 6-8 consecutive measurements prior to surgery (baseline IOP) and weekly after treatment, using a calibrated Tonolab tonometer. Animals were either treated with delta opioid-receptor agonist, SNC-121 (1 mg/kg; i.p) or Br-cAMP (1 mg/kg; i.p), daily for 7 days. Pattern electroretinograms (PERG), retinal ganglion cells (RGCs) in flat mount, and axons were counted 4-6 week post injury. The changes in the expression patterns of PI3K/Akt and phospho-cyclic AMP-response element binding protein (p-CREB) were determined by Western blotting and immunohistochemistry.

Results: Glaucomatous injury caused significant (p<0.05) reduction in pattern ERG (PERG), axonal, and RGC numbers at 6th week, post glaucomatous injury. PERG deficits, axonal, and RGC survival were significantly improved by SNC-121 treatment. A sustained (7-42 days, post injury) decline in PI3K/Akt and CREB phosphorylation is seen in the glaucomatous retina and optic nerve, which was reversed by SNC-121 treatment. Classically, opioid-receptors are linked to pertussis toxin sensitive Gi proteins which inhibit adenylyl cyclase activity and attenuate cAMP formation. However, our data prompted us to believe that either δ-opioid receptors are linked to Gs proteins or opioid-receptor-activation leads to AC superactivation for cAMP production. Thus we measured the levels of cAMP at day 42 post glaucomatous injury in untreated and SNC-121 treated rats. The level of cAMP was decreased by 29% in glaucomatous retinas. Surprisingly, we have seen an increase in the production of cAMP in SNC-121-treated normal and glaucomatous eyes. Additionally, we found that Br-cAMP increases axonal transport, RGC neuroprotection, and CREB phosphorylation.

Conclusions: These data provide evidence that PI3K/Akt and CREB, a transcription factor, are the potential neuroprotective downstream targets of δ-opioid-receptors for RGC neuroprotection. Data also provide novel information about the linkage of δ-opioid-receptors with Gs-proteins and/or AC superactivation, which will open new avenues for RGC neuroprotection.


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