ArticleProceedings of the National Academy of Sciences of the United States of America1997
Glutamine synthetase protects against neuronal degeneration in injured retinal tissue.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 133 citations in OpenAlex.
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- Protein Degradome of Spinal Cord Injury: Biomarkers and Potential Therapeutic Targets.Molecular neurobiology · 2020Review
- Photoreceptor Degeneration Accompanies Vascular Changes in a Zebrafish Model of Diabetic Retinopathy.Investigative ophthalmology & visual science · 2020Article
- Loss of MPC1 reprograms retinal metabolism to impair visual function.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
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- Whole-eye electrical stimulation therapy preserves visual function and structure in P23H-1 rats.Experimental eye research · 2016Article
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- Why are astrocytes important?Neurochemical research · 2015Review
- Neurodegeneration as a primary change and role of neuroprotection in diabetic retinopathy.Molecular neurobiology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neurotransmitter glutamate is neurotoxic when it is accumulated in a massive amount in the extracellular fluid. Excessive release of glutamate has been shown to be a major cause of neuronal degeneration after central nervous system injury. Under normal conditions, accumulation of synaptically released glutamate is prevented, at least in part, by a glial uptake system in which the glia-specific enzyme glutamine synthetase (GS) plays a key role. We postulated that glial cells cannot cope with glutamate neurotoxicity because the level of GS is not high enough to catalyze the excessive amounts of glutamate released by damaged neurons. We examined whether elevation of GS expression in glial cells protects against neuronal degeneration in injured retinal tissue. Analysis of lactate dehydrogenase efflux, DNA fragmentation, and histological sections revealed that hormonal induction of the endogenous GS gene in retinal glial cells correlates with a decline in neuronal degeneration, whereas inhibition of GS activity by methionine sulfoximine leads to increased cell death. A supply of purified GS enzyme to the culture medium of retinal explants or directly to the embryo in ovo causes a dose-dependent decline in the extent of cell death. These results show that GS is a potent neuroprotectant and that elevation of GS expression in glial cells activates an endogenous mechanism whereby neurons are protected from the deleterious effects of excess glutamate in extracellular fluid after trauma or ischemia. Our results suggest new approaches to the clinical handling of neuronal degeneration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.