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Rejeana M. Stephens, Paige C. McIntyre, Rajat Sethi, Carlos A. Garcia; Ozone Decreases Dopamine Levels and Disrupts the Circadian Clock in the Rat Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):918.
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Dopaminergic cells in the inner retina and melatonin synthesizing photoreceptor cells of the outer retina play opposing roles in the regulation of retinal adaptive physiology and are under circadian control. Additionally, the Period1(Per1) clock gene is expressed in dopaminergic cells. Ozone (O3) is a major component of urban air pollution that has been reported to diminish acetylcholine levels in the preoptic area in the rat brain leading to disruption of paradoxical sleep. The purpose of this study is to test the hypothesis that O3 alters retinal circadian rhythmicity by decreasing dopamine levels and interfering with Per1 gene expression in the retinas of Long Evans rats.
Age and sex-matched rats were randomly separated into four groups (n=4); one control (clean air) and three O3-exposed groups (0.4 ppm for 4 hours; 1 day, 7 days, and 14 days). Upon completion of the exposures, the neural retinas of the O3-exposed and age and sex-matched control rats were collected for dopamine and Per1 analysis. The levels of dopamine and its metabolites, homovanillic acid and DOPAC were measured by HPLC. Per1 expression was done by extracting total RNA, and the samples then reverse transcribed and subjected to RT-PCR analysis using the appropriate primers.
The dopamine, homovanillic acid and DOPAC content significantly decreased (p< 0.05) in the retinas of the 7-day and 14-day ozone-exposed groups as compared to controls, and the Per1 gene transcript was altered in the retinas of all the O3 -exposed groups tested.
Results of this study provide evidence that O3 disrupts the retinal circadian clock by decreasing dopamine levels and altering the expression of the Per1 gene. Additional physiological functions such as photoreceptor rod outer segment disc shedding, synaptic dynamics, protein phosphorylation, gene expression and melatonin synthesis may be impacted by ozone.
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