March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Enhancement of -Opioidergic-Receptor Activity Provides Retina Neuroprotection Against Glaucomatous Injury
Author Affiliations & Notes
  • Yasir Abdul
    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; Shahid Husain, None
  • Footnotes
    Support  NIH (EY-019081)
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1960. doi:
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      Yasir Abdul, Shahid Husain; Enhancement of -Opioidergic-Receptor Activity Provides Retina Neuroprotection Against Glaucomatous Injury. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1960.

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

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Purpose: : This study was designed to determine the neuroprotective activity of Δ-opioid-receptors and associated cellular mechanisms against glaucomatous injury in a chronic glaucoma rat model.

Methods: : Brown Norway rats were used to elevate intraocular pressure (IOP) by injecting 50 µL of 2 M 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 treated with Δ-opioid-receptor agonist, SNC-121 (1mg/kg; i.p.), daily for 7 days. Pattern electroretinograms (PERG) and retinal ganglion cells (RGCs) in flat-mounts were counted at week-8 post injury. The expression of TNF-α and MMP-9 were determined by immunohistochemistry (IHC) on day-7, post injury.

Results: : Significant IOP elevation was seen as early as 7 days, and maintained for up to 8 weeks, post injury. PERG amplitudes were significantly reduced in ocular-hypertensive eyes (14.03±0.69 µvolts) when compared to normal eyes (18.38±0.69 µvolts) at week-8, post injury. PERG deficits in hypertensive eyes were significantly improved by SNC-121 treatment (17.35±1.76 µvolts; P<0.05). There was a 26% loss of RGCs in the hypertensive eye when compared to the normal eye at week-8, post injury. The loss in RGCs was fully blocked when animals were treated with SNC-121. To dissect out the early cellular events during glaucomatous injury, retinal samples were analyzed for TNF-α, MMP-9, and NF-ΚB at day-7, post injury. In ocular hypertensive eyes TNF-α, MMP-9, and NF-ΚB were several-fold up-regulated. Both TNF-α and MMP-9 were inhibited in SNC-121 treated ocular hypertensive eyes.

Conclusions: : These data provide concrete evidence that enhancement of Δ-opioidergic-receptor activity by exogenous ligand provides retina neuroprotection against glaucomatous injury. Mechanistic data provide clues that TNF-α and MMP-9 are produced in the early phase of injury and suppressed by activation of Δ-opioid-receptors. These findings support the idea that enhancement of Δ-opioidergic activity in the eye may present a viable neuroprotective strategy for the treatment of glaucoma.

Keywords: intraocular pressure • neuroprotection • retina: neurochemistry 

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