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Yasir Abdul, Shahid Husain; Roles of Nitric Oxide in Delta Opioid-Receptor Agonist (SNC 121) Mediated Retina Neuroprotection in Chronic Glaucoma Rat Model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6335.
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To determine the roles of nitric oxide in SNC-121-mediated retina neuroprotection in chronic glaucoma rat model.
Intraocular pressure (IOP) was raised in Brown Norway rats by injecting 50 μL of 2M hypertonic saline into the circumferential limbal veins. Inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine hydrochloride (AG; 25mg/kg; i.p.), was administered right after the hypertonic saline injections and subsequently once a day for 7 days. Alternatively, SNC-121 (1 mg/kg; i.p) was administered right after the injury or 1 hour post AG treatment. IOP was measured weekly after hypertonic saline injection. Pattern electroretinograms (PERG) were recorded at 2, 4, and 6 weeks, pots injury. Retrograde labeling of retinal ganglion cells (RGCs) was performed using Fluorogold. The expression pattern of nitric oxide synthase in retina and optic nerve samples was determined by immunohistochemistry and Western blotting.
We have seen a 31% increase in IOP in hypertonic saline-injected eyes at week 6th, post injury. The IOP was not changed either by aminoguanidine (AG) or SNC-121 treatment. The PERG amplitudes and RGCs were reduced to 74±4% and 82±4 %, respectively, in ocular-hypertensive eyes. The PERG were improved to 97±4% (n=6; p<0.01) and 90 ± 7% (n=6; p<0.047) when animals were treated with SNC-121 or AG, respectively. Additionally, we have seen a synergistic effect on PERG amplitudes (119 ± 8%; n=6; p<0.001) when animals were treated with both AG and SNC-121 simultaneously. Additionally, the survival rate of RGCs was increased when animals were treated with SNC-121 or AG. We also have seen an increase in the nitric oxide synthase (NOS) expression in ocular-hypertensive eyes, which was further reduced in SNC-121 treated animals.
Controversial reports have been published for the role of nitric oxide in the retina neuroprotection in several glaucoma model. Our data suggest that blockage of iNOS activity directly by AG or indirectly by SNC-121 is beneficial, which subsequently provide retina neuroprotection against glaucomatous injury. Additionally, data provide clues that SNC-121-mediated retina neuroprotection is mediated via inhibition of multiple pathways. Data also indicated that nitric oxide-dependent pathway is one of the potential targets of SNC-121-mediated retina neuroprotection.
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