Abstract—Age is a leading risk factor for the development of age-related macular degeneration (AMD), which is the cause of vision loss in the elderly. There are no effective methods of therapy for this complex neurodegenerative disease due to the incomplete knowledge of its etiology and pathogenesis. It is assumed that development of an aging imbalance of neurotransmitter systems (glutamate and GABA) in the retina, their desynchronosis, may be a precondition for the development progression of AMD. Information about their state in the retina during aging, and especially development of AMD, is extremely limited. We previously assessed age-related changes in the daytime glutamate/GABA system in the retinas of Wistar and senescence-accelerated OXYS rats that develop AMD-like pathology. Here, we evaluated aging changes in the synthesis and degradation enzymes, receptor subunits, and transporters of these neurotransmitters at nighttime and compared them with detected earlier in the daytime. Differences in age-related changes in the expression of the components of the glutamate and GABAergic systems at night and daytime were revealed during “healthy” aging in Wistar rats and during premature aging in OXYS rats. This may be due to disruption of the circadian rhythm. It has been established that the progression of AMD-like retinopathy in OXYS rats occurs against the background of changes in the glutamatergic system at the nighttime (increased glutamine synthetase and NMDARr1 levels and a decreased GLAST level), which facilitate retinal neurodegenerative changes. Pronounced changes in the GABAergic system, which could make a significant contribution to the development of the pathological process, were not identified.
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ACKNOWLEDGMENTS
The animals were provided by Common facilities “Gene pools of laboratory animals” of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences.
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This work was supported by the Russian Science Foundation grant no. 21-75-00029.
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Ethical Approval. All applicable international, national and/or institutional guidelines for the care and use of animals have been followed. The studies were approved by the ethics committee of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences (Novosibirsk, Russia; No. 34 dated June 15, 2016).
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Corresponding authors; address: pr. Ak. Lavrentiev 10, Novosibirsk, 630090 Russia; e-mail: telegina@bionet.nsc.ru.
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Telegina, D.V., Antonenko, A.K. & Kolosova, N.G. Differences in Changes in the Glutamate/GABA System Activity in the Rat Retina during Aging and the Development of Retinopathy at Nighttime and Daytime. Neurochem. J. 17, 380–386 (2023). https://doi.org/10.1134/S1819712423030170
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DOI: https://doi.org/10.1134/S1819712423030170
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Abbreviations:
- AMD, age-related macular degeneration
- RPE, retinal pigment epithelium
- SCN, suprachiasmatic nucleus
- AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
- GABAAr1, r1 subunit of the GABA receptor
- GABA-T, GABA transaminase
- GAD67, an isoform of glutamate decarboxylase
- GAPDH, glyceraldehyde-3-phosphate dehydrogenase
- GAT1, GABA transporter 1
- GLAST, glutamate-aspartate transporter
- NMDAr1, subunit r1 of the N-methyl-D-aspartate receptor