Melanopsin‐expressing ganglion cells on macaque and human retinas form two morphologically distinct populations

Abstract

The long-term goal of this research is to understand how retinal ganglion cells that express the photopigment melanopsin, also known as OPN4, contribute to vision in humans and other primates. Here we report the results of anatomical studies using our polyclonal antibody specifically against human melanopsin that confirm and extend previous descriptions of melanopsin cells in primates. In macaque and human retina, two distinct populations of melanopsin cells were distinguished based on dendritic stratification in either the inner or outer portion of the inner plexiform layer (IPL) . Variation in dendritic field size and cell density with eccentricity was confirmed, and dendritic spines, a new feature of melanopsin cells, were described. The spines were the sites of input from DB6 diffuse bipolar cell axon terminals to the inner stratifying type of melanopsin cells. The outer stratifying melanopsin type received inputs from DB6 bipolar cells via the DB6 cell’s bistratified outer axonal processes. Outer stratifying melanopsin cells also received inputs from axon terminals of dopaminergic amacrine cells. On the outer stratifying melanopsin cells, ribbon synapses from bipolar cells and conventional synapses from amacrine cells were identified in electron-microscopic immunolabeling experiments. Both inner and outer stratifying melanopsin cell types were retrogradely labeled following tracer injection in the lateral geniculate nucleus (LGN). In addition, a method for targeting melanopsin cells for intracellular injection using their intrinsic fluorescence was developed. This technique was used to demonstrate that melanopsin cells were tracer-coupled to amacrine cells and would be applicable to electrophysiological experiments in the future.

Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

“…Intrinsically photosensitive retinal ganglion cells (ipRGCs) (Berson 2003;Berson, Dunn & Takao 2002;Dacey et al 2005) are a specific group of melanopsin expressing ganglion cells with cell bodies in the ganglion cell layer (GCL) and dendrites that stratify in the sublaminae of the inner plexiform layer (IPL) (Dacey et al 2005) (Figure 1.1). At least five ipRGC subtypes (M 1 -M 5 ) have been identified in animal models (Schmidt et al 2011b) however only M 1 and M 2 subtypes have been identified in humans and primates (Jusuf, Lee, Hannibal & Grünert 2007;Liao et al 2016) (Figure 1.1).…”

“…Their large dendritic trees spiral around the foveal pit to form an extensive plexus and the dendrites stratify within either the inner or outer borders of the inner plexiform layer (IPL) (Dacey et al 2005). (Jusuf et al 2007;Liao et al 2016). …”

“…At least five different ipRGC subtypes (M 1 -M 5 ) (Ecker et al 2010;Schmidt et al 2011a) have been identified that project to non-image forming centres in the rodent brain, with the M 1 and M 2 subtypes likely to be homologous to the outer and inner stratifying melanopsin cells found in humans and non-human primates (Dacey et al 2005;Jusuf et al 2007;Liao et al 2016). A recent mouse study using single M 1 ipRGC axonal tracing and confocal microscopic analysis identified up to five different brain targets that received input from a single M 1 subtype ipRGC, indicating that a single ipRGC can affect brain areas involved in numerous lightmediated behaviours (Fernandez, Chang, Hattar & Chen 2016).…”

An Evaluation of Melanopsin Function and Light Exposure in Depressive Disorders

“…Melanopsin-expressing retinal ganglion cells were subsequently identified in non-human primates and in human's retinae (Dacey, Liao, Peterson, Robinson, Smith, Pokorny, Yau, & Gamlin, 2005) and these cells constitute 0.2% (~3,000) in the primates and 0.4% (~4,400) human retinae (Liao, Ren, Peterson, Marshak, Yau, Gamlin, & Dacey, 2016).…”

“…They can be histologically differentiated in the retina from the midget and parasol ganglion cells of the parvocellular and magnocellular pathway, based on their large cell bodies (diameter 19±3 µm to 23±3 µm in human) and dendritic trees (diameter 646±151 µm to 690±148 um in human) which arborise in the inner plexiform layer (Dacey et al, 2005;Liao et al, 2016). The dendritic field diameter in both human and macaque retinae increases from the fovea to the periphery with the dendritic field diameter in both human and macaque retina increasing from ~250 µm at the fovea to ~1200 µm at ~16 mm of retinal eccentricity with dendrites at the fovea forming a plexus surrounding the foveal pit (Dacey et al, 2005;Jusuf, Lee, Hannibal, & Grünert, 2007;Liao et al, 2016). The peak ipRGC density decreases from the fovea (30-35 cells/mm 2 ) to the peripheral retina (8-10 cells/mm 2 ) through ~16 mm of retinal eccentricity in the human retina (Liao et al, 2016).…”