Light regulation of retinal dopamine that is independent of melanopsin phototransduction

Abstract

Light dependent release of dopamine (DA) in the retina is an important component of light-adaptation mechanisms. Melanopsin-containing inner retinal photoreceptors have been shown to make physical contacts with DA amacrine cells and have been implicated in the regulation of the local retinal environment in both physiological and anatomical studies. Here we determined whether they contribute to photic regulation of DA in the retina as assayed by the ratio of DA with its primary metabolite, DOPAC, and by c-fos induction in tyrosine hydroxylase (TH) labeled DA amacrine cells. Light treatment (∼0.7 log W/m2 for 90min) resulted in a substantial increase in DA release (as revealed by an increase in DOPAC:DA ratio) as well as widespread induction of nuclear c-fos in DA amacrine cells in wild type mice and in mice lacking melanopsin (Opn4-/-). Light induced DA release was also retained in mice lacking rod phototransduction (Gnat1-/-), although the magnitude of this response was substantially reduced compared to wild-types, as was the incidence of light-dependent nuclear c-fos in DAergic amacrines. By contrast, the DAergic system of mice lacking both rods and cones (rd/rd cl) showed no detectable light response. Our data suggest that light regulation of DA, a pivotal retinal neuromodulator, originates primarily with rods and cones and that melanopsin is neither necessary nor sufficient for this photoresponse.

Visually-Driven Ocular Growth in Mice Requires Functional Rod Photoreceptors

“…4C; Student's ttest, t ¼ 3.24, P ¼ 0.01). 33 However, the DA levels in WT and Gnat1 À/À mice were similar between the genotypes and different light phases (Fig. 4B).…”

“…Light regulation of dopamine levels is mainly through rods, cones, and possibly melanopsin cells. [32][33][34] Dopamine increases in a log-linear relationship with illuminance, [35][36][37] although these studies did not examine rod-isolating illuminance levels. Moreover, rod pathways and the dopaminergic system interact structurally and functionally; for instance, DA neurons synapse onto AII and A17 amacrine cells in the rod pathway, rod-driven ON pathways stimulate DA release, which in turn decrease rod function as the retina adapts to daylight function, and loss of rods results in decreased DA levels in the retina.…”

Protective effects of the neuropeptide PACAP in diabetic retinopathy

“…Dopaminergic amacrine cells can activate cones through type D2 dopamine receptors. They have also been implicated in the regulation of the local retinal environment (Cameron et al 2009). The degeneration of dopaminergic amacrine cells disables the cross-talk between scotopic and photopic signaling pathways in photoreceptor cells and in the whole retinal circuity.…”

Melanopsin and inner retinal photoreception

“…Consequently, this pathway would be well placed to translate melanopsin activation into modifications in retinal physiology. It should be noted, however, that melanopsin phototransduction does not appear either necessary or sufficient for large-scale dopamine release in the retina [71].…”