title: Delta-opioid agonist SNC-121 protects retinal ganglion cell function in a chronic ocular hypertensive rat model.
abstract: OBJECTIVE
  This study examined if the delta-opioid (δ-opioid) receptor agonist, SNC-121, can improve retinal function and retinal ganglion cell (RGC) survival during glaucomatous injury in a chronic ocular hypertensive rat model.
  
  
  METHODS
  IOP was raised in brown Norway rats by injecting hypertonic saline into the limbal venous system. Rats were treated with 1 mg/kg SNC-121 (intraperitoneally [IP]) once daily for 7 days. Pattern-electroretinograms (PERGs) were obtained in response to contrast reversal of patterned visual stimuli. RGCs were visualized by fluorogold retrograde labeling. Expression of TNF-α and p38 mitogen-activated protein (MAP) kinase was measured by immunohistochemistry and Western blotting.
  
  
  RESULTS
  PERG amplitudes in ocular hypertensive eyes were significantly reduced (14.3 ± 0.60 μvolts) when compared with healthy eyes (18.0 ± 0.62 μvolts). PERG loss in hypertensive eyes was inhibited by SNC-121 treatment (17.20 ± 0.1.3 μvolts; P < 0.05). There was a 29% loss of RGCs in the ocular hypertensive eye, which was inhibited in the presence of SNC-121. TNF-α production and activation of p38 MAP kinase in retinal sections and optic nerve samples were upregulated in ocular hypertensive eyes and inhibited in the presence of SNC-121. Furthermore, TNF-α induced increase in p38 MAP kinase activation in astrocytes was inhibited in the presence of SNC-121.
  
  
  CONCLUSIONS
  These data provide evidence that activation of δ-opioid receptors inhibited the loss of PERG amplitudes and rate of RGC loss during glaucomatous injury. Mechanistic data provided clues that TNF-α is mainly produced from glial cells and activates p38 MAP kinase, which was significantly inhibited by SNC-121 treatment. Overall, data indicate that enhancement of δ-opioidergic activity in the eye may provide retina neuroprotection against glaucoma.
authors: Hewitt Laboratory of the Ola B. Williams Glaucoma Center, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: Yasir
authors: Y
authors: Abdul
authors: Naseem
authors: N
authors: Akhter
authors: Shahid
authors: S
authors: Husain
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001549:Benzamides / Q000627:therapeutic use*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002908:Chronic Disease; D019610:Cytoprotection; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007429:Intraocular Pressure / Q000502:physiology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009798:Ocular Hypertension / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009898:Optic Disk / Q000166:cytology; D010879:Piperazines / Q000627:therapeutic use*; D051381:Rats; D011914:Rats, Inbred BN; D017465:Receptors, Opioid, delta / Q000819:agonists*; D012160:Retina / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001549:Benzamides; D018696:Neuroprotective Agents; D010879:Piperazines; D017465:Receptors, Opioid, delta; D014409:Tumor Necrosis Factor-alpha; C102990:SNC 121; D048051:p38 Mitogen-Activated Protein Kinases
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