Abstract
Purpose: :
The release of dopamine (DA) in the retina is influenced both by an endogenous circadian clock and by light, and forms part of the mechanism by which retinal physiology is optimised according to time of day and prior light exposure. In view of the importance of melanopsin photoreception in defining circadian and diurnal physiology, and the direct interaction between the dendrites of ipRGCs and DA amacrines (Vugler et al., 2007, Exp Neurol. 205, 26), we set out to evaluate whether it also contributes to this local retinal event.
Methods: :
Eyes were collected from rodless+coneless (rd/rd cl) and melanopsin knockout (Opn4-/-) mice, and their congenic wild-type controls at subjective midnight or midday (6 or 18hrs dark adapted respectively) with or without exposure to white light (~3.5 log W/m2) for 90min . One retina was dissected for HPLC analysis of DA and DOPAC. The other was fixed with PFA and 10µm sections processed for dual labelled immunohistochemistry using antisera recognising tyrosine hydroxylase (TH) and c-fos.
Results: :
Congenic wild-type controls for both transgenic genotypes showed a light-dependent increase in the DOPAC:DA ratio at both midday and midnight indicating enhanced DA release. They also exhibited a strong increase in c-fos immunoreactivity in TH expressing amacrines. Both of these light responses were observed in Opn4-/- mice and indeed had magnitudes indistinguishable from that of wild types. By contrast, rd/rd cl mice failed to show light dependent changes in either DOPAC:DA ratio or in c-fos expression in TH amacrine cells.
Conclusions: :
Melanopsin phototransduction is neither necessary nor sufficient for the light-dependent activation of c-fos in DA amacrines and the release of DA. This implies that outer-retinal photoreceptors alone are responsible for photic regulation of DA amacrines.
Keywords: dopamine • amacrine cells • retina: proximal (bipolar, amacrine, and ganglion cells)