Preservation of retina ganglion cell function by morphine in a chronic ocular-hypertensive rat model.
OBJECTIVE
The current study examined if opioid-receptor-activation by morphine can improve retinal function and retinal ganglion cell (RGC) integrity in a chronic glaucoma rat model.


METHODS
IOP was raised in Brown Norway rats by injecting hypertonic saline into the limbal venous system. Rats were treated daily with 1 mg/kg morphine for 28 days at 24-hour intervals; animals were examined for changes in IOP by a TonoLab tonometer. Pattern-ERG (PERG) was obtained in response to contrast-reversal of patterned visual stimuli. RGCs were visualized by fluorogold retrograde-labeling. Changes in the expression pattern of TNF-α and caspases were measured by Western blotting.


RESULTS
A significant IOP elevation was seen as early as 7 days, and maintained for up to 8 weeks, after surgery. PERG amplitudes were significantly reduced in ocular-hypertensive eyes (15.84±0.74 μvolts) when compared with normal eyes (19±0.86 μvolts). PERG deficits in hypertensive eyes were reversed by morphine treatment (18.23±0.78 μvolts; P<0.05). In untreated rats, a 24% reduction in labeled RGCs was measured in the hypertensive eye compared with the normal eye. This reduction in RGC labeling was significantly ameliorated in the presence of morphine. In retinal samples, TNF-α, caspase-8, and caspase-3 expressions were significantly upregulated in ocular hypertensive eyes, but completely inhibited in the morphine-treated animals.


CONCLUSIONS
These data provide evidence that activation of opioid receptors can provide significant improvement in PERG and RGC integrity against glaucomatous injury. Mechanistic data provide clues that activation of one or more opioid receptors can reduce glaucomatous-injury via suppression of TNF-α and caspase activation.
Hewitt Laboratory of the Ola B. Williams Glaucoma Center, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina 29425, USA. Husain@musc.edu
Shahid
S
Husain
Yasir
Y
Abdul
Craig E
CE
Crosson
D000701:Analgesics, Opioid / Q000627:therapeutic use; D000818:Animals; D015153:Blotting, Western; D020169:Caspases / Q000096:biosynthesis; D002470:Cell Survival; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D004596:Electroretinography; D005260:Female; D005500:Follow-Up Studies; D007429:Intraocular Pressure; D008297:Male; D009020:Morphine / Q000627:therapeutic use*; D009798:Ocular Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011914:Rats, Inbred BN; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000701:Analgesics, Opioid; D014409:Tumor Necrosis Factor-alpha; D009020:Morphine; D020169:Caspases