Melanopsin-expressing retinal ganglion cells are intrinsically photosensitive cells that are involved in non-image forming visual processes such as the pupillary light reflex and circadian entrainment but also contribute to visual perception. Here we used immunohistochemistry to study the morphology, density, distribution, and synaptic connectivity of melanopsin-expressing ganglion cells in four post mortem human donor retinas. Two types of melanopsin-expressing ganglion cells were distinguished based on their dendritic stratification near either the outer or the inner border of the inner plexiform layer. Outer stratifying cells make up on average 60% of the melanopsin-expressing cells. About half of the melanopsin-expressing cells (or 80% of the outer stratifying cells) have their soma displaced to the inner nuclear layer. Inner stratifying cells have their soma exclusively in the ganglion cell layer and include a small proportion of bistratified cells. The dendritic field diameter of melanopsin-expressing cells ranges from 250 (near the fovea) to 1,000 µm in peripheral retina. The dendritic trees of outer stratifying cells cover the retina independent of soma location. The dendritic fields of both outer and inner stratifying cells show a high degree of overlap with a coverage factor of approximately two. Melanopsin-expressing cells occur at an average peak density of between ∼20 and ∼40 cells/mm at about 2 mm eccentricity, the density drops to below ∼10 cells/mm at about 8 mm eccentricity. Both the outer and inner stratifying dendrites express postsynaptic density (PSD95) immunoreactive puncta suggesting that they receive synaptic input from bipolar cells.

In primates, the retinal ganglion cells contributing to high acuity spatial vision (midget cells and parasol cells), and blue‐yellow color vision (small bistratified cells) are well understood. Many other ganglion cell types with large dendritic fields (named wide‐field ganglion cells) have been identified, but their spatial density and distribution are largely unknown. Here we took advantage of the recently established molecular diversity of ganglion cells to study wide‐field ganglion cell populations in three primate species. We used antibodies against the transcription factor Special AT‐rich binding protein 2 (Satb2) to explore its expression in macaque (Macaca fascicularis, M. nemestrina), human and marmoset (Callithrix jacchus) retinas. In all three species, Satb2 cells make up a low proportion (1.5–4%) of the ganglion cell population, with a slight increase from central to peripheral retina. Intracellular dye injections revealed that in macaque and human retinas, the large majority (over 80%) of Satb2 cells are inner and outer stratifying large sparse cells. By contrast, in marmoset retina the majority (over 60%) of Satb2 expressing cells were broad thorny cells, with smaller proportions of recursive bistratified (putative direction‐selective), large bistratified, and outer stratifying narrow thorny cells. Our findings imply that Satb2 expression has undergone rapid species specific adaptations during primate evolution, because expression is not conserved across Old World (macaque, human) and New World (marmoset) suborders.

Recent advances in single-cell RNA sequencing have enabled the molecular distinction of ganglion cell populations in mammalian retinas. Here we used antibodies against the transcription factor special AT-rich binding protein 1 (Satb1, a protein which is expressed by on-off direction-selective ganglion cells in mouse retina) to study Satb1 expression in the retina of marmosets (Callithrix jacchus), macaques (Macaca fascicularis), and humans. In all species, Satb1 was exclusively expressed in retinal ganglion cells. The Satb1 cells made up ∼2% of the ganglion cell population in the central retina of all species, rising to a maximum ∼7% in peripheral marmoset retina. Intracellular injections in marmoset and macaque retinas revealed that most Satb1 expressing ganglion cells are widefield ganglion cells. In marmoset, Satb1 cells have a densely branching dendritic tree and include broad and narrow thorny, recursive bistratified, and parasol cells, all of which show some costratification with the outer or inner cholinergic amacrine cells. The recursive bistratified cells showed the strongest costratification but did not show extensive cofasciculation as reported for on-off direction-selective ganglion cells in rabbit and rodent retinas. In macaque, Satb1 was not expressed in recursive bistratified cells, but in large sparsely branching cells. Our findings further support the idea that the expression of transcription factors in retinal ganglion cells is not conserved across Old World (human and macaque) and New World (marmoset)primates and provides a further step to link a molecular marker with specific cell types.