Author(s): Dennis M. Dacey (corresponding author) [1]; Hsi-Wen Liao [2]; Beth B. Peterson [1]; Farrel R. Robinson [1]; Vivianne C. Smith [3]; Joel Pokorny [3]; King-Wai Yau [2]; Paul D. Gamlin [4]
Human vision starts with the activation of rod photoreceptors in dim light and short (S)-, medium (M)-, and long (L)- wavelength-sensitive cone photoreceptors in daylight. Recently a parallel, non-rod, non-cone photoreceptive pathway, arising from a population of retinal ganglion cells, was discovered in nocturnal rodents [1]. These ganglion cells express the putative photopigment melanopsin and by signalling gross changes in light intensity serve the subconscious, 'non-image-forming' functions of circadian photoentrainment and pupil constriction [1, 2, 3, 4, 5, 6, 7]. Here we show an anatomically distinct population of 'giant', melanopsin-expressing ganglion cells in the primate retina that, in addition to being intrinsically photosensitive, are strongly activated by rods and cones, and display a rare, S-Off, (L + M)-On type of colour-opponent receptive field. The intrinsic, rod and (L + M) cone-derived light responses combine in these giant cells to signal irradiance over the full dynamic range of human vision. In accordance with cone-based colour opponency, the giant cells project to the lateral geniculate nucleus, the thalamic relay to primary visual cortex. Thus, in the diurnal trichromatic primate, 'non-image-forming' and conventional 'image-forming' retinal pathways are merged, and the melanopsin-based signal might contribute to conscious visual perception.
There is evidence that a melanopsin-associated photodetective pathway exists in the diurnal human visual system [8, 9, 10, 11, 12], similar to the one found in the nocturnal rodent. However, the detailed anatomical and functional properties of a melanopsin pathway in primates, and its relationship to rod and cone circuits, are unknown. To identify the melanopsin-expressing cells in the primate, a polyclonal antibody derived from the conceptually translated, full-length complementary DNA for the human melanopsin protein was used to immunostain human and macaque retinae. In flat mounts of the entire retina, the melanopsin antisera revealed a morphologically distinct population of [similar]3,000 retinal ganglion cells with completely stained cell bodies, dendritic trees and axons (Fig. 1a-c). With [similar]1.5 million ganglion cells in the human retina, the melanopsin-expressing cells comprise only 0.2% of the total. The melanopsin-expressing ganglion cell bodies were big, giving rise to the largest dendritic tree diameters of any primate retinal ganglion cell identified thus far [13] (Fig. 1d-f). The long, sparsely branching dendrites produced an extensive meshwork of highly overlapping processes. Cell counts showed a shallow density gradient ranging from 3-5 cells mm-2 over much of the retinal periphery to a peak of 20-25 cells mm-2 in the parafoveal retina (Fig. 1g); in contrast, total ganglion cells reach a peak density of [similar]50,000 cells mm-2 . In the central retina, the extremely large dendritic trees of melanopsin-containing ganglion cells spiralled around the foveal pit to form an extensive plexus (Fig. 1e). Melanopsin-containing dendrites were localized to two strata: the extreme inner and extreme outer borders of the inner plexiform layer (Fig. 1h). Individual cells are principally monostratified, creating two distinct subpopulations...