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Shahid Husain; Preservation of Retinal Ganglion Cells Function by Opioids in Rat Glaucoma Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2660.
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© ARVO (1962-2015); The Authors (2016-present)
To determine if opioid-receptor-activation preserves retinal ganglion cell function and modifies the expression pattern of TNF-α and MMP-9 in a rat glaucoma model.
Brown Norway rats were used to elevate intraocular pressure (IOP) by injecting 50 µL of 2M hypertonic saline into the circumferential limbal veins near the cornea. 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. Pattern electroretinograms (PERG) were recorded using black and white alternating contrast reversing-bars with spatial frequency of 0.033 cycles/degree and reversal frequency of 1 Hz using the UTAS-2000 system. The expression of TNF-α and MMP-9 was determined using immunohistochemistry and Western blot analyses.
IOP remained elevated in the hypertonic saline-treated eye when compared to the contralateral eye, up to 8 weeks post surgery. Initial mean baseline IOP (Day 0) was 18.25 ±0.45 mmHg for control eyes. The mean IOP in the treated eye was 26.13 ±0.95 mmHg on Day 56 (P <0.05). PERG amplitudes were significantly (P <0.05) reduced in ocular-hypertensive eyes when compared with control eyes at 8 weeks. To determine if opioid-receptor-activation during glaucomatous injury preserved the function of retinal ganglion cells (RGCs), animals were treated with opioid-receptor agonists (0.1-1 mg/kg morphine, SNC-121; i.p.) each day for 7-28 days. Opioid treatment preserves the RGC function significantly (P <0.05), as determined by PERG. To evaluate the cellular events during glaucomatous injury, changes in TNF-α and MMP-9 expression in ONH tissues were analyzed at week-8, post injury. TNF-α was increased more than 3-fold over the control level, which was significantly different (P <0.05) from the control eye at week-8, post injury. Additionally, there was a robust increase in MMP-9 production in glaucomatous eyes when compared with normal contralateral eyes.
These results provide evidence that activation of the opioidergic system preserved RGC function, as determined by PERG. These data provide the initial evidence that TNF-α and MMP-9 are up-regulated in the optic nerve head (ONH) during glaucomatous injury. Excessive production of TNF-α and MMPs leads to optic nerve injury and subsequently RGC death. Opioid-receptor activation counterbalances the detrimental actions by suppressing production of TNF-α and MMP-9 within the ONH. Overall, these results provide evidence that the opioidergic system exhibits the potential to protect the retina against glaucomatous injury.
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