Retinal Glutamate Neurotransmission: From Physiology to Pathophysiological Mechanisms of Retinal Ganglion Cell Degeneration
Abstract
:1. Retinal Network Integration Requires Glutamate Neurotransmission
2. Distribution of Glutamate Receptors and Transporters in the Retinas
2.1. Ionotropic Receptors
2.2. Metabotropic Receptors
2.3. Glutamate Transporters
3. Vulnerability of the Retina and RGCs to Disease
4. Glutamate Excitotoxicity in the Retina
4.1. Impairment in Glutamate Clearance and the Role of Müller Glia
4.2. Glutamate Receptor-Induced RGC Degeneration
4.3. Factors Affecting NMDA Receptor-Mediated Degeneration
5. Cellular Mechanisms of NMDA Receptor-Induced Excitotoxicity in RGCs
5.1. Intracellular Calcium Dysregulation
5.2. Imbalance of Signalling Pathways and Gene Expression
5.3. Mitochondrial Dysfunction
5.4. Endoplasmic Reticular Stress
6. Final Remarks and Therapeutic Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Ionotropic Glutamate Receptors | Metabotropic Glutamate Receptors | Glutamate Transporters | |||
---|---|---|---|---|---|
AMPA Receptors (GluA1-2) | Kainate Receptors (GluK1-5) | NMDA Receptors (GluN1, 2A-D, 3A-B) | Group I-III Metabotropic Receptors (mGluR1-8) | EAAT1-5 xCT | |
Photoreceptors | - | GluK5 only presynaptic [28] | GluN1, 2B only presynaptic [29,30] | mGluR8 [31] | EAAT2 [24,32] EAAT5 [33] |
Horizontal cells | GluA2-4 [26] | - | GluN1 [29,34]/ additional subunits unknown | - | EAAT3 [32,35] |
Bipolar cells | GluA1-4 [22] | GluK1 (OFF-BCs) [36] GluK1-3 [22,37] | GluN1,2C-D [23,37] GluN2D only presynaptic in rod BCs [29,38] | mGluR6 (ON-BCs) [17] mGluR8 [39,40] mGluR7 presynaptic [40,41] | EAAT2 [24,32] EAAT3 [32,35] EAAT5 [33] |
Amacrine cells | GluA1-4 [22,26] | GluK2-5 [22,26,37] GluD1-2 [42] | GluN1,2A-C [29,37] | mGluR1 [22] mGluR2 [43] mGluR5 [44] mGluR7 postsynaptic [40,41] | EAAT2 [24,32] EAAT3 [32,35] |
Retinal ganglion cells | GluA1-4 [22,26] | GluK2-5 [22,26,37] | GluN1,2-C [23,26,29,37] GluN3A [45] | mGluR1 [22] | EAAT3 [32,35] |
Müllerglia | AMPA receptor (in vitro) [46] * GluA4 [22] | - | NMDA receptor (in vitro) [47,48] * | - | EAAT1 [24,32,48] EAAT4 [49] xCT [50] |
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Boccuni, I.; Fairless, R. Retinal Glutamate Neurotransmission: From Physiology to Pathophysiological Mechanisms of Retinal Ganglion Cell Degeneration. Life 2022, 12, 638. https://doi.org/10.3390/life12050638
Boccuni I, Fairless R. Retinal Glutamate Neurotransmission: From Physiology to Pathophysiological Mechanisms of Retinal Ganglion Cell Degeneration. Life. 2022; 12(5):638. https://doi.org/10.3390/life12050638
Chicago/Turabian StyleBoccuni, Isabella, and Richard Fairless. 2022. "Retinal Glutamate Neurotransmission: From Physiology to Pathophysiological Mechanisms of Retinal Ganglion Cell Degeneration" Life 12, no. 5: 638. https://doi.org/10.3390/life12050638