Retinal Dopamine Mediates Multiple Dimensions of Light-Adapted Vision

Abstract

Dopamine is a key neuromodulator in the retina and brain that supports motor, cognitive and visual function. Here, we developed a mouse model, on a C57 background, in which expression of the rate-limiting enzyme for dopamine synthesis, tyrosine hydroxylase, is specifically disrupted in the retina. This model enabled assessment of the overall role of retinal dopamine in vision using electrophysiological (electroretinogram), psychophysical (optokinetic tracking) and pharmacological techniques. Significant disruptions were observed in high-resolution, light-adapted vision caused by specific deficits in light responses, contrast sensitivity, acuity and circadian rhythms in this retinal dopamine-depleted mouse model. These global effects of retinal dopamine on vision are driven by the differential actions of dopamine D1 and D4 receptors on specific retinal functions and appear to be due to the ongoing bioavailability of dopamine, rather than developmental effects. Taken together, our data indicate that dopamine is necessary for the circadian nature of light-adapted vision, as well as optimal contrast detection and acuity.

Dopamine D1 Receptors Contribute Critically to the Apomorphine-Induced Inhibition of Form-Deprivation Myopia in Mice

“…45 We also found that suppression of the b-wave and summed OP amplitudes by the D1R antagonist SCH39166 resembled the ERG phenotype of the D1R-KO mice. Similar results showing a reduction of the b-wave amplitude have been obtained by other authors working with D1R-KO mice 44,46,47 and D1R antagonist-treated goldfish. 41 However, in frogs, pharmacologic blockage of D1Rs increased the amplitudes of b-waves of both dark-and light-adapted ERGs.…”

Circadian Rhythm of Contrast Sensitivity Is Regulated by a Dopamine–Neuronal PAS-Domain Protein 2–Adenylyl Cyclase 1 Signaling Pathway in Retinal Ganglion Cells

“…We previously determined that optimal daytime contrast sensitivity requires dopamine and D4Rs (Jackson et al, 2012). Therefore, we examined the expression of Npas2 mRNA in the GCL of mice lacking D4Rs (Drd4 Ϫ / Ϫ mice).…”

“…Dopamine, through dopamine receptor subtype 4 (D4R), modulates contrast sensitivity, and dopamine deficiency in the retina alone is sufficient to cause contrast sensitivity deficits (Jackson et al, 2012). However, the underlying cellular and molecular mechanisms through which retinal dopamine modulates contrast sensitivity have not been elucidated.…”

Role of Melatonin and Dopamine in the Regulation of Retinal Circadian Rhythms

“…Thus, it is unlikely that D 2 R activation induces Per1 mRNA via the cAMP signaling pathway. Per1 mRNA induction in the retina may be regulated by cAMP-independent signaling pathways since photic induction of Per1 mRNA is dramatically decreased in D 2 R −/− mice [ 126 ] and a functional CRE is not required for its induction [ 128 ] (see Fig. 4.4 ).…”

“…In wild-type mice, the b-wave amplitude is higher in the daytime than at night and this difference persists in constant darkness [ 134 , 135 ]. The ERG rhythm is disrupted in Bmal1 and Cry mutant mice [ 134 , 135 ], and in mice with a conditional retina-specifi c disruption of Th (RetTH-KO), that depletes dopamine from the retina but not the brain [ 126 ]. The effect of retinal dopamine depletion is phenocopied in mice lacking dopamine D 4 receptors and the circadian rhythm of photopic ERG can be induced in RetTH-KO mice by daily injection of a dopamine D 4 receptor agonist.…”