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C.J. Destache, C.A. Opere, H. Liu, M. Zhao, G. Zhan, S.E. Ohia; Effect of 8–iso–PGE2 on Rabbit Anterior Uveal Catecholamines, in vivo . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2614.
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We have previously shown that isoprostanes can modulate sympathetic neurotransmission in isolated bovine irides (Opere et al., Free Rad. Res. 35: 2001). It is, however unclear if isoprostanes can regulate the release of endogenous catecholamines from mammalian anterior uvea, in vivo.
To determine the effect of intravitreally injected 8–isoprostaglandin (PG)E2 on endogenous catecholamine levels of aqueous humor and iris–ciliary bodies (ICB) in rabbits, in vivo.
Albino rabbits (New Zealand strain; 2Kg) were sedated with intramuscular ketamine and xylazine, then injected intravitreally with 8–isoPGE2. Control eyes received an equal volume of vehicle. After 4 hours, animals were sacrificed painlessly with CO2 gas. Aqueous humor and ICB were withdrawn and isolated for measurement of catecholamine levels and their metabolites using High Pressure Liquid Chromatography with electrochemical detection. DHBA was used as the internal standard to integrate peak area of the neurotransmitters.
In the ICB, intravitreally injected 8–isoPGE2 (0.1µM and 10µM) increased dopamine levels by 306% and 477%; (p<0.001), respectively. Norepinephrine was increased by 127% at 0.1µM 8–isoPGE2 but decreased by 45% at 10µM concentration of the isoprostane. The dopamine metabolite, 3,4–dihydroxyphenylacetic acid (DOPAC) was increased by 211% and 164%; (p<0.001) at 0.1µM and 10µM 8–isoPGE2, respectively. In the aqueous humor, 8–isoPGE2 (0.1µM and 10µM) decreased dopamine levels by 83% and 56%; (p<0.01), respectively while norepinephrine was increased by 50% at the 10µM concentration. Interestingly, the metabolites DOPAC and HIAA were increased within the same concentration range.
We conclude that intravitreal injections of 8–isoPGE2 can alter both ICB and aqueous humor catecholamine and serotonin levels in vivo. An effect of this isoprostane on anterior uveal catecholamine concentrations may underlie its mechanism of action on aqueous humor dynamics.
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