Localization, distribution, and connectivity of neuropeptide Y in the human and porcine retinas—A comparative study

Abstract

Neuropeptide Y (NPY) is a peptide neurotransmitter abundantly expressed in the mammalian retina. Since its discovery, NPY has been studied in retinas of several species, but detailed characterization of morphology, cell-type, and connectivity has never been conducted in larger mammals including humans and pigs. As the pig due to size and cellular composition is a well-suited animal for retinal research, we chose to compare the endogenous NPY system of the human retina to that of pigs to support future research in this field. In the present study, using immunohistochemistry, confocal microscopy and 3D reconstructions, we found NPY to be expressed in GABAergic and calretinin-immunoreactive (-ir) amacrine cells of both species as well as parvalbumin-ir amacrine cells of humans. Furthermore, we identified at least two different types of medium- to wide-field NPY-ir amacrine cells. Finally, we detected likely synaptic appositions between the NPY-ir amacrine cells and melanopsin- and nonmelanopsin-ir ganglion cells, GABAergic and dopaminergic amacrine cells, rod bipolar cells, and horizontal cells, suggesting that NPY-ir cells play diverse roles in modulation of both image and non-image forming retinal signaling. These findings extend existing knowledge on NPY and NPY-expressing cells in the human and porcine retina showing a high degree of comparability. The extensive distribution and connectivity of NPY-ir cells described in the present study further highlights the potential importance of NPY signaling in retinal function.

Neuropeptide Y facilitates P2X1 receptor-dependent vasoconstriction via Y1 receptor activation in small mesenteric arteries during sympathetic neurogenic responses

“…The incidence of NPY acting directly as a vasoconstrictor is highly variable across species and vascular beds studied. NPY has direct vasoconstrictor effects on human forearm arteries [21], canine coronary arteries [46] and porcine superior retinal arteries [10], but not human pulmonary arteries [11]. Mixed response have been reported for rat mesenteric arteries [3,40].…”

“…Co-signalling by all three neurotransmitters at vascular smooth muscle cells contributes to the neurogenic contractile response, though the degree of contribution can vary dependent upon vascular bed, stimulus strength and disease state [9,27,47]. Norepinephrine and ATP consistently act as neurotransmitters with primary trophic effects, whilst the effect of neuronally released NPY is highly variable and can have primary trophic or post-junctional modulatory effects [3,10]. Circulating NPY is increased in patients with hypertension, cardiac hypertrophy and heart failure [23,36,50].…”

Relevance of Peptide Homeostasis in Metabolic Retinal Degenerative Disorders: Curative Potential in Genetically Modified Mice

“…In the mouse retina, NPY is expressed by both ACs and displaced ACs (dAC), which is very similar to the labelling experienced in rats ( Sinclair and Nirenberg, 2001 ). In the human retina, NPY is also expressed by ACs and dACs ( Christiansen et al, 2018a ).…”

Expression of SH3 and Multiple Ankyrin Repeat Domains Protein 3 in Mouse Retina

“…As previously mentioned, the cells in the GCL could be GCs or displaced ACs. To determine if GCs indeed express SHANK3, we used a specific GCs marker, Brn3a, to perform doublelabeling with SHANK3 (Sato et al, 2017;Christiansen et al, 2018). The merged image (Figure 6a") reveals that the Brn3apositive GCs in the GCL expressed SHANK3 because the two label colors (somata, stained red by Brn3a; membranes, stained green by SHANK3) perfectly fit into each other.…”