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M. Zhao, C. B. Toris, S. E. Ohia, C. A. Opere; Regulation of Retinal Endogenous Excitatory Neurotransmitters by Isoprostanes: Role of EP-Receptors. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6244.
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© ARVO (1962-2015); The Authors (2016-present)
We investigated the effect of the isoprostane, 8-isoprostaglandin E2 (8-isoPGE2) on endogenous levels of excitatory amino acid neurotransmitter glutamate and its metabolite, glutamine in the bovine retina, ex vivo
Freshly isolated bovine eyeballs were injected intravitreally with either vehicle (for control) or 8-isoPGE2 (0.01µM -100µM) and retina and vitreous humors were isolated 30 min after treatment for measurement of amino acids using High Performance Liquid Chromatography
8-isoPGE2 caused a concentration-dependent reduction of retinal glutamate and glutamine levels. For instance, 8-isoPGE2 (1 µM and 100 µM) significantly (p<0.001) attenuated retinal glutamate levels by 34% and 48%, respectively. Likewise, 8-isoPGE2 (100 µM) inhibited retinal glutamine levels by 38% (p<0.01). On the other hand, 8-isoPGE2 exhibited no effect on glutamine levels in the vitreous humor. Glutamate was not detected either before or after 8-isoPGE2 treatment in vitreous humor. Pretreated bovine eyeballs with the enzyme inhibitors flurbiprofen (nonselective COX inhibitor), NS-398 (selective COX-2 inhibitor) or furegrelate (thromboxane synthase inhibitor) did not interfere with the inhibitory effects of 8-isoPGE2 on retinal glutamate and glutamine concentrations. To determine the role of prostanoid receptors in the inhibitory effects of 8-isoPGE2, eyeballs were pretreated with the prostanoid receptor antagonists SC-19220 (EP1), AH-6809 (EP1/2/3), AH-23848 (EP4) or SQ-29548 (TP). SC-19220, AH-6809 and AH-23848 blocked the inhibitory effects of 8-isoPGE2 on retinal glutamate and glutamine levels in a concentration-dependent manner. Interestingly, the TP antagonist, SQ-29548 did not prevent the inhibitory effects of 8-isoPGE2. Used as a positive control, the EP receptor agonist, PGE2 (10 µM) reduced retinal glutamate and glutamine levels by 48% (p<0.001) and 45% (p<0.001), respectively and its effects were reversed by both SC-19220 and AH-6809
The isoprostane, 8-isoPGE2 can decrease the levels of endogenous excitatory neurotransmitter, glutamate and its metabolite glutamine in bovine retina, ex vivo presumably via an effect on EP-receptors. This finding suggests a potential neuroprotective effect of 8-isoPGE2 in mammalian retina.
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