Ionotropic glutamate receptors in the retina – a bioinformatical meta-analysis

Abstract

Glutamate is an essential neurotransmitter for signal processing in the vertical pathway of the mammalian retina, where it is involved in the distribution of visual information into several parallel channels. The excitatory effects of glutamate are mediated by AMPA-, kainate-, and NMDA-type ionotropic glutamate receptors (iGluRs). The expression patterns of these receptors in the vertebrate retina have been investigated so far with mainly immunocytochemical, in-situ hybridization, and electrophysiological/pharmacological techniques. Here, we have used scRNA sequencing data from chicken, mouse, macaque, and human retina to describe and compare the profile of iGluR expression in major retinal cell types across species. Our results suggest that major retinal cell types each express a unique set of iGluRs with substantial differences between non-mammalian and mammalian retinae. Expression of iGluRs has been investigated in more detail for amacrine and bipolar cell types of the human retina, each showing minor variations of a common pattern. The differential expression of iGluRs is likely to convey unique signal processing properties to individual elements of the retinal circuitry.

Retinal Glutamate Neurotransmission: From Physiology to Pathophysiological Mechanisms of Retinal Ganglion Cell Degeneration

“…Table 1 summarises the complex pattern of receptor subunits and transporter subtypes in different retinal cells, which mirrors the intricate mechanisms involved in retinal glutamatergic neurotransmission. Additional and more recent investigations shed light on the genomic and transcriptomic expression of different receptor subunits which appear to be similar in rodent and primate retinas [ 26 , 27 ]. Hence, the following paragraphs aim to depict a general and up-to-date picture of glutamate receptor and transporter distribution according to studies conducted on either rodent or primate retinas.…”

“…iGluRs are differentially expressed throughout the retina [ 22 , 26 , 29 ]. PCs express GluN1, GluN2B and GluK5 subunits at their presynaptic terminals [ 29 , 30 ].…”

“…Although little is known about glutamatergic responses of horizontal cells, they are thought to be mediated preferentially through AMPA receptors [ 34 , 69 ] (in particular, GluA2-4 subunits), but they do not express any functional kainate receptors [ 26 ]. In addition, GluN1 has been shown to be expressed in horizontal cells but, to date, no functional evidence of this NMDA receptor subunit has been reported [ 29 , 34 ].…”

“…Amacrine cells also express NMDA receptor subunits (GluN1,2A-C) [ 29 , 37 ], though the differential distribution of GluN2A and GluN2B subunits within the IPL indicate their involvement in different retinal circuits [ 29 ]. For instance, glutamatergic amacrine cells show predominant expression of the GluN2A subunit, whereas cholinergic amacrine cells express GluN2B [ 26 ]. Extrasynaptic GluN2B-containing NMDA receptors are found also to modulate the glycinergic AII amacrine cell response in the cone pathway, whereas GABAergic A17 amacrine cells express GluN2A-containing NMDA receptors which mediate rod pathway neurotransmission [ 72 ].…”

“…RGCs show predominant expression of NMDA (GluN1,2A-C), AMPA (GluA1-4) and kainate receptors (GluK2-5) [ 22 , 26 , 29 , 37 ] with differential synaptic and extrasynaptic localization. In particular, non-NMDA receptors are believed to be the main responders to the synaptic quantal release of glutamate [ 73 , 74 , 75 ], whereas NMDA receptors are mainly located at peri- and extrasynaptic sites, where they react to ambient glutamate levels and, hence, their activity is enhanced by reductions in glutamate uptake [ 76 , 77 ].…”