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M. Zhao, H. Liu, C.J. Destache, G. Zhan, S.E. Ohia, D.A. Opere, C.A. Opere; Regulation of Rabbit Retinal and Vitreous Humor Neurotransmitter Levels by 8–isoPGF2, in vivo . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3770.
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Evidence from our laboratory demonstrates that isoprostanes can modulate excitatory amino acid neurotransmission in isolated bovine retinae (Opere et al., Neurochem. Res. 30:2005).
To determine the effect of intravitreally injected 8–isoprostaglandin (PG)F2α on retinal and vitreous humor catecholamine levels in rabbits, in vivo. We also examined the effect of intravitreally administered 8–isoPGF2α on serotonin concentrations in the retina and vitreous humor.
Albino rabbits (New Zealand strain; 2 kg) were sedated with intramuscular ketamine and xylazine, then injected intravitreally with 8–isoPGF2α. Control eyes received an equal volume of vehicle. After 4 hours, animals were sacrificed painlessly with CO2 gas. Retinae and vitreous humor were isolated for measurement of catecholamine and serotonin and their metabolites using HPLC–ECD system.
Intravitreally administered 8–isoPGF2α (0.1 to 10 µM) attenuated dopamine, norepinephrine and serotonin levels in the retina. For instance, at 10 µM, 8–isoPGF2α attenuated dopamine, norepinephrine and serotonin levels by 51 % (p<0.01), 27 % (p<0.01) and 19 % respectively. With the exception of serotonin metabolite 5–hydroxyindole acetic acid (HIAA), 8–isoPGF2α also decreased retinal content of catecholamine metabolites 3,4–dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). In the vitreous humor, 8–isoPGF2α (0.1µM) inhibited dopamine, DOPAC and HIAA by 36 %(p<0.01), 36 % (p<0.01) and 33 % (p<0.01) respectively. Interestingly, serotonin and norepinephrine were not detected in the vitreous humor after administration of 8–isoPGF2α.
We conclude that 8–isoPGF2α can regulate catecholamine and serotonin concentrations in the rabbit retina and vitreous humor, in vivo. The mechanism that underlies isoprostane–induced changes in neurotransmitter levels in the retina and vitreous humor merits further investigation.
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