Neurotoxic Reactive Astrocytes Drive Neuronal Death after Retinal Injury
Open accessAbstract
Glaucoma is a neurodegenerative disease that features the death of retinal ganglion cells (RGCs) in the retina, often as a result of prolonged increases in intraocular pressure. We show that preventing the formation of neuroinflammatory reactive astrocytes prevents the death of RGCs normally seen in a mouse model of glaucoma. Furthermore, we show that these spared RGCs are electrophysiologically functional and thus still have potential value for the function and regeneration of the retina. Finally, we demonstrate that the death of RGCs depends on a combination of both an injury to the neurons and the presence of reactive astrocytes, suggesting a model that may explain why reactive astrocytes are toxic only in some circumstances. Altogether, these findings highlight reactive astrocytes as drivers of RGC death in a chronic neurodegenerative disease of the eye.
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In vivo, genomic deletion of Il1a, Tnf, and C1qa prevented death of retinal ganglion cell (RGC) neurons after optic nerve crush (ONC) or in the bead occlusion model of glaucoma.
“In vivo, genomic deletion of Il1a, Tnf, and C1qa prevented death of retinal ganglion cell (RGC) neurons after optic nerve crush (ONC) or in the bead occlusion model of glaucoma3”
From Neurotoxic reactive astrocytes induce cell death via saturated lipids (2021) · cites this paper as [3]
Elovl1 cKO mice still showed neuronal death following ONC, unlike Il1a−/−Tnf−/−C1qa−/− mice, which show no RGC death following axon crush, but the amount of death was reduced.
“While Elovl1 cKO mice still showed neuronal death following ONC (unlike in Il1a−/−Tnf−/−C1qa−/− mice, which show no RGC death following axon crush2,3,20), the amount of death was reduced”
From Neurotoxic reactive astrocytes induce cell death via saturated lipids (2021) · cites this paper as [3]
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- Authors
- Guttenplan, K. A., Stafford, B. K., El-Danaf, R. N., Adler, D. I., Münch, A. E., Weigel, M. K., Huberman, A. D., & Liddelow, S. A.
- Affiliations
- Stanford Medicine (US)
- Salk Institute for Biological Studies (US)
- New York University Abu Dhabi (AE)
- NYU Langone Health (US)
- Corresponding author
- Guttenplan, Kevin A.
- Liddelow, Shane A.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 31
- Issue
- 12
- Pages
- 107776
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC8091906
- OpenAlex
- W3037075657
- Cited by
- 221
- References
- 50
- Citations by year
- 2026: 23 · 2025: 30 · 2024: 39 · 2023: 36 · 2022: 48 · 2021: 34 · 2020: 10
- FWCI
- 25.38
- Type
- journal article
- Language
- en
- Update notices
- erratum (2024-06-25)
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NYU Grossman School of Medicine
- Cure Alzheimer's Fund
- Glenn Foundation for Medical Research
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- reactive astrocytes, neurotoxicity, retinal ganglion cells, glaucoma, retinal damage, neuronal cell death, neuroinflammation, intraocular pressure, retinal regeneration, electrophysiological function
- MeSH terms
- Animals, Astrocytes, Axons, Dendrites, Disease Models, Animal, Glaucoma, Gliosis, Interleukin-1, Intraocular Pressure, Microspheres, Neurons, Neurotoxins, Retina, Retinal Ganglion Cells, Tumor Necrosis Factor-alpha, Complement C1q, Cell Death, Mice, Knockout, Cell Shape
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