April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Neuroprotective Targets of Delta Opioid-Receptor in Glaucoma
Author Affiliations & Notes
  • Shahid Husain
    Ophthalmology, Medical Univ of South Carolina, Charleston, SC
  • Yasir Abdul
    Ophthalmology, Medical Univ of South Carolina, Charleston, SC
  • Sudha Singh
    Ophthalmology, Medical Univ of South Carolina, Charleston, SC
  • Carolyn Peterseim
    Ophthalmology, Medical Univ of South Carolina, Charleston, SC
  • Footnotes
    Commercial Relationships Shahid Husain, None; Yasir Abdul, None; Sudha Singh, None; Carolyn Peterseim, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2180. doi:
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      Shahid Husain, Yasir Abdul, Sudha Singh, Carolyn Peterseim; Neuroprotective Targets of Delta Opioid-Receptor in Glaucoma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2180.

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

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Purpose: This study was designed to determine the downstream targets of delta opioid-receptors for neuroprotection in 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 or SNC-80 (1 mg/kg; i.p) or Br-cAMP (1 mg/kg; i.p), daily for 7 days. Pattern electroretinograms (PERG), retinal ganglion cells 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: PERG amplitudes were significantly reduced in ocular-hypertensive eyes (16.78±1.23 µvolts) when compared to normal eyes (22.24±1.42 µvolts) the 6th week, post injury. PERG deficits in hypertensive eyes were significantly improved by SNC-121 treatment (21.70±1.03 µvolts; P<0.05). There was a significant loss of RGCs and axons in the hypertensive eyes and the loss in RGCs and axons was fully blocked in SNC-121-treated animals by the 6th week, post injury. We found that SNC-121 activate and phosphorylate PI3K/Akt pathway and cyclic AMP-response element binding protein (CREB). A PI3K/Akt inhibitor, LY-294002 (1 mg/kg), fully blocked SNC-121 mediated retina neuroprotection. Moreover, PERG were significantly improved by Br-cAMP treatment when measured on 6th week, post injury.

Conclusions: These data provide initial evidence that PI3K/Akt and CREB, a transcription factor, are the potential neuroprotective targets of delta opioid-receptors in glaucomatous injury. Data also provide clues that PI3K/Akt pathway and CREB may have negatively regulated the neurodegenerative pathways in SNC-121-induced retina neuroprotection.

Keywords: 615 neuroprotection • 688 retina • 715 signal transduction: pharmacology/physiology  

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