Retinal glutamate receptor

Retinal ganglion cells are the output cells of the refina. Their axons course along the vitreal surface of the refina and bundle together to exit the eye as the optic nerve. Ganglion cells are excited by glutamate released from bipolar cells acting on both NMDA and non-NMDA (KA- and AMPA-type) glutamate receptors (Thoreson and Witkovsky, 1999). 

Thoreson WB, Witkovsky P (1999) Glutamate receptors and circuits in the vertebrate retina. Prog Retin Eye Res 18 765-810. 

Nakajima, Y., Iwakabe, H., Akazawa, C., el al. (1993) Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate. Journal of Biological Chemistry, 268, 11868-11873. 

Brandstatter JH, Koulen P, Kuhn R, Van der Putten H, Wassle H (1996) Compartmental localization of a metabotropic glutamate receptor (mGluR7) two different active sites at a retinal synapse. J Neuwsci 76 4749-4756. 

Godwin DW, Van Horn SC. Erisir A. Sesma M, Romano C, Sherman SM (1996) Ultrastructural localization suggests that retinal and cortical inputs access different metabotropic glutamate receptors in the lateral geniculate nucleus. J Neurosci /d 8181-8192. 

Glutamate s role as a neurotransmitter in the vertebrate retina is reviewed by Barnstable (1993), Brandstatter et al. (1998) and Lo et al. (1998). As the cell bodies of different retinal cell types are in different laminae (Fig. 10), we can assign which general cell types express which glutamate receptor subunits. However, there are different subsets of the same cell class, e.g., there are at least 10 different types of on- and off-bipolars, and multiple subtypes of the other cell classes (Stevens, 1998). Without cell-type markers and double-labelling studies, ISH can not differentiate these. The cones and rods release glutamate onto the bipolar cells only off-bipolars use ionotropic receptors at this synapse on-bipolars use the metabotropic receptor mGluR6 instead. The distribution of NMDA and non-NMDA receptor mRNAs in the retina is summarized in Fig. 10. 

As desensitisation is a prominent feature of AMPA receptors, a plant lectin, concanavilin A, previously shown to block desensitisation of insect glutamate receptors [54], was tested and found to enhance AMPA and kainate responses on hippocampal [43, 66], retinal [67] and dorsal root ganglion (DRG) [68] neurones. More recently, a series of benzothiazides including diazoxide and cyclothiazide, were shown to reduce glutamate receptor desensitisation and hence increase AMPA responses on hippocampal [69, 70] and cortical [71] neurones. As will be discussed below, it has become clear that concanavilin A and cyclothiazide act selectively on rapidly inactivating kainate and AMPA responses respectively. 

There is considerable evidence that overstimulation of glutamate receptors promotes cell death in a number of retinal disease processes. Glutamate overstimulation may be particularly important in acute ischemic injuries, but it also may play a role in diabetic retinopathy (16) and chronic neurodegenerative processes such as glaucoma (17). Evidence for this includes the observation that glutamate levels are elevated in the vitreous of patients with these conditions (16,17). 

Retinal ischemic injury, for example, has been shown to result in the overstimulation of ionotropic glutamate receptors following the extracellular accumulation of glutamate (18,19). This effect appears to involve, in particular, the NMDA class of glutamate receptors. The subsequent excessive influx of calcium results in... 

Eye function It protects retinal neurons against N-methyl-D-aspartate receptor mediated glutamate neurotoxicity. Deterioration of accommodation following visual work has also been shown to improve in individuals receiving methylcobalamin. 

Yang, X. L. (2004). Characterization of receptors for glutamate and GABA in retinal neurons. Prog. Neurobiol. 73, 127-150. 

Muller cells are major sites for the uptake and removal of neurotransmitters, most notably glutamate and GABA. Glutamate transport into neurons is smaller and slower than transport into Muller cells and thus uptake into Muller cells is the principal mechanism responsible for the initial removal of extracellular glutamate following synaptic activation (Pow, 2001). In addition to neurotransmitter transporters, Muller cells possess neurotransmitter receptors and can release neuroactive substances (e.g., ATP) (Newman, 2004). Thus, activity of retinal neurons can influence Muller cells and Muller cell activity can in turn influence adjacent neurons. 

Retinal circuitry is further refined by ehminating inappropriate synapses. Glutamate, through NMDA receptors, is known to be involved in synaptic pruning in the CNS, and there is evidence that it also does so in the retina. 

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