Amino acid neurochemistry of the vertebrate retina

Kalloniatis, Michael; Tomisich, Guido

doi:10.1016/s1350-9462(98)00036-6

Cited by 106 publications

(116 citation statements)

References 300 publications

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“…4C). Interestingly, the localization of mNAT2 expression is consistent with that of free glutamine, which has been previously shown to occur at the highest levels in ganglion cells and their axons (30,31). To further confirm the expression of mNAT2 in the nerve fibers of ganglion cells, we examined the localization of mNAT2 in the optic papilla (optic disc) where ganglion cell axons converge to form the optic nerve (Fig.…”

Section: Fig 2 Hydrophobicity and Inferred Topology Of Mnat2supporting

confidence: 67%

“…Hence, glutamine serves as a precursor for the generation of glutamate in these cells (19,20). In the previously reported studies using a glutamine immunoreactivity assay, the presence of free glutamine was most abundantly identified in glutamatergic ganglion cells and their axons in comparison to all other retinal cells (30,31). Remarkably, the localization pattern of glutamine in the retina matches that of mNAT2 expression.…”

Section: Discussionsupporting

confidence: 52%

“…We measured efflux of (16,17). Notice that free glutamine is most abundant in NFL/GCL layers as shown by other investigators (30,31). mNAT2 mediates the transport of free glutamine into axons of ganglion (G) cells.…”

Section: Fig 2 Hydrophobicity and Inferred Topology Of Mnat2mentioning

confidence: 74%

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Characterization of an N-system Amino Acid Transporter Expressed in Retina and Its Involvement in Glutamine Transport

Gu¹,

Roderick

Camacho

et al. 2001

Journal of Biological Chemistry

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We report here on the characterization of a mouse N-system amino acid transporter protein, which is involved in the transport of glutamine. This protein of 485 amino acids shares 52% sequence homology with an Nsystem amino acid transporter, mouse N-system amino acid transporter (mNAT) and its orthologs. Because this protein shares a high degree of sequence homology and functional similarity to mNAT, we named it mNAT2. mNAT2 is predominately expressed in the retina and to a slightly lesser extent in the brain. In the retina, it is located in the axons of ganglion cells in the nerve fiber layer and in the bundles of the optic nerve. Functional analysis of mNAT2 expressed in Xenopus oocytes revealed that the strongest transport activities were specific for L-glutamine. In addition, mNAT2 is a Na ؉ -and pH-dependent, high affinity transporter and partially tolerates substitution of Na ؉ by Li ؉ . Additionally, mNAT2 functions as a carrier-mediated transporter that facilitates efflux. The unique expression pattern and selective glutamine transport properties of mNAT2 suggest that it plays a specific role in the uptake of glutamine involved in the generation of the neurotransmitter glutamate in retina.

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Section: Fig 2 Hydrophobicity and Inferred Topology Of Mnat2supporting

confidence: 67%

Section: Discussionsupporting

confidence: 52%

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Characterization of an N-system Amino Acid Transporter Expressed in Retina and Its Involvement in Glutamine Transport

Gu¹,

Roderick

Camacho

et al. 2001

Journal of Biological Chemistry

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“…Altered glutamate metabolism and transamination reactions associated with ischaemia could also account for the elevated levels of aspartate, which is a metabolite/precursor for glutamate. 49 Both of these explanations can account for the observed positive association between aspartate and glutamate levels in SRF. Aspartate may also act as a neurotoxin, 50 acting through NMDA receptors in a fashion similar to glutamate.…”

Section: Discussionmentioning

confidence: 99%

Amino-acid levels in subretinal and vitreous fluid of patients with retinal detachment

Bertram

Bula

Pulido

et al. 2007

Eye

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Purpose To compare the concentration of amino acids in subretinal and vitreous fluid of patients with primary rhegmatogenous retinal detachment to that of control vitreous. Methods This prospective, observational study measured amino-acid levels in subretinal fluid of patients undergoing scleral buckle placement (n ¼ 20) and vitreous fluid in patients undergoing pars plana vitrectomy (n ¼ 5) for primary retinal detachment. Vitreous fluid from patients undergoing vitrectomy for macular hole (n ¼ 7) or epiretinal membrane (n ¼ 3) served as a control. Subretinal fluid and control vitreous were analysed using high-pressure liquid chromatography. Retinal detachment vitreous was analysed using capillary electrophoresis-laser-induced fluorescence. Results Mean levels of glutamate (27.071.7 lM), aspartate (4.174.0 lM), and glycine (44.1731.0 lM) in subretinal fluid and glutamate (13.4711.9 lM) in the vitreous were significantly elevated in retinal detachment compared to control vitreous. A significant, positive association was observed between levels of aspartate and glutamate in subretinal fluid (Spearman's correlation coefficient: 0.74, Po0.01). Mean arginine levels did not differ significantly between subretinal fluid and control vitreous. Levels of alanine, tyrosine, valine, isoleucine, leucine, and phenylalanine were significantly lower in subretinal fluid compared to control vitreous (all Po0.01). Conclusions Glutamate levels in subretinal fluid and vitreous of patients with primary retinal detachment is significantly elevated in comparison to control vitreous. This finding lends further support to the hypothesis that elevated glutamate levels may result from ischaemia of the outer retina secondary to retinal detachment.

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“…The cone transmitter is glutamate (Massey, 1990;Kalloniatis and Tomisich, 1999;Thoreson and Witkovsky, 1999), which is released at the ribbons that position the vesicles to the region of exocytosis (Rao-Mirotznik et al, 1995). From the release sites, glutamate has to diffuse for quite some distance to exert its effect at the three postsynaptic structures mentioned above: the invaginating and flat contacts and the desmosome-like junctions .…”

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confidence: 99%

The Synaptic Architecture of AMPA Receptors at the Cone Pedicle of the Primate Retina

2001

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Cone pedicles, the output synapses of cone photoreceptors, transfer the light signal onto the dendrites of bipolar and horizontal cells. Cone pedicles contain between 20 and 45 ribbon synapses (triads) which are the release sites for glutamate, the cone transmitter. Several hundred postsynaptic dendrites contact individual cone pedicles, and we studied the glutamate receptors expressed and clustered at these contacts, particularly the AMPA receptor subunits.Using immunocytochemistry and confocal imaging we were able to resolve individual triads within the cone pedicles by light microscopy. We studied their differences in L/M-and S-cones, and we counted the number of triads per pedicle across the retina. The presynaptic matrix protein bassoon, the synapseassociated membrane protein P84, and peanut agglutinin were used to specifically label synaptic ribbons, invaginating dendrites of horizontal cells and invaginating dendrites of ON-cone bipolar cells, respectively.Pre-and post-embedding immunocytochemistry and electron microscopy were used to localize the AMPA receptor subunits at the cone pedicle base. They were aggregated at three different postsynaptic sites: at horizontal cell invaginating contacts, at bipolar cell flat contacts, and at desmosome-like junctions underneath the cone pedicles.We also performed double-labeling experiments with the triad-specific markers and the antibodies against the AMPA receptor subunits. AMPA receptors were preferentially expressed by horizontal cells, and to a lesser extent by OFF-cone bipolar cells. We did not observe any cone-selective expression of AMPA receptor subunits postsynaptic to L/M-or S-cones, suggesting AMPA receptors are not the key to understanding trichromatic signaling in the primate retina.

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Amino acid neurochemistry of the vertebrate retina

Cited by 106 publications

References 300 publications

Characterization of an N-system Amino Acid Transporter Expressed in Retina and Its Involvement in Glutamine Transport

Characterization of an N-system Amino Acid Transporter Expressed in Retina and Its Involvement in Glutamine Transport

Amino-acid levels in subretinal and vitreous fluid of patients with retinal detachment

The Synaptic Architecture of AMPA Receptors at the Cone Pedicle of the Primate Retina

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