The Role of the Classical Complement Cascade in Synapse Loss During Development and Glaucoma
Abstract
Glaucoma is one of the leading causes of vision loss worldwide, yet the signals that initiate the progressive degeneration of optic nerve axons and the selective loss of retinal ganglion neurons (RGCs) remain elusive. Reactive gliosis, release of inflammatory cytokines, and complement upregulation all occur in the early stages of glaucoma in several disease models. Recent work has implicated the classical complement cascade in the elimination of excess synaptic connections in the developing visual system and in early synapse loss associated with glaucoma, suggesting that mechanisms of developmental synapse elimination may be aberrantly re-activated in glaucoma. This review describes current evidence in support of this "synaptic" hypothesis and places complement in the context of other well-described mechanisms of neurodegeneration occurring in the glaucomatous eye.
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Abnormal microglia function and complement cascade activation have been associated with neurodegeneration of the CNS.
“Consistent with this idea, abnormal microglia function and complement cascade activation have been associated with neurodegeneration of the CNS (Alexander et al., 2008; Beggs and Salter, 2010; Rosen and Stevens, 2010; Schafer and Stevens, 2010; Stephan et al. 2012).”
From Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner (2012) · cites this paper as Rosen and Stevens, 2010
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Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
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“Furthermore, given that microglia are the only CNS cell that express CR3 in the postnatal dLGN, these data suggest that microglia are mediators of synaptic remodeling in Neuron 74, 691–705, May 24, 2012 ª2012 Elsevier Inc. 699 (A) Single plane array tomography images for VGlut2 (green) to label RGC terminals and GluR1…”
InfluentialSelf-citationMicroglia in Alzheimer’s disease
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“CD2AP Adaptor protein between membrane proteins and actin cytoskeleton Interactions with SHIP1 and RIN3 (Bao et al., 2012; Rouka et al., 2015) suggest role in microglia endocytosis.”
BackgroundThe Complement System: An Unexpected Role in Synaptic Pruning During Development and Disease
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Self-citationThe molecular basis of retinal ganglion cell death in glaucoma
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Self-citationInflammation in Glaucoma: From the back to the front of the eye, and beyond
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Complement, a target for therapy in inflammatory and degenerative diseases
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Complement in neurological disorders and emerging complement-targeted therapeutics
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Complement in health and disease
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The Complex Role of Neuroinflammation in GlaucomaPreprint
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Complement C1q‐C3–associated synaptic changes in multiple sclerosis hippocampus
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Wnts in action: from synapse formation to synaptic maintenance
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The Pathogenesis of Glaucoma in the Interplay with the Immune System
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Deficiency of complement component 5 ameliorates glaucoma in DBA/2J mice
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Central nervous system diseases related to pathological microglial phagocytosis
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Synapse Loss and Dendrite Remodeling in a Mouse Model of Glaucoma
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Clusterin and Complement Activation in Exfoliation Glaucoma
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Stem cells in managing glaucoma
Cappellani, F., Capobianco, M., Visalli, F., Avitabile, A., Gagliano, G., Nicolosi, S. G., Khouyyi, M., D’Esposito, F., Gagliano, C., & Zeppieri, M. (2026) · World Journal of Stem Cells · doi:10.4252/wjsc.120083
- Authors
- Rosen, A. M., & Stevens, B.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Stevens, Beth
- ORCID
- Stevens, Beth
- Venue
- Advances in Experimental Medicine and Biology
- Publisher
- Springer New York
- Published
- 2010
- Volume
- 703
- Pages
- 75-93
- ISSN
- 0065-2598 (ISSN-L)
- OpenAlex
- W96660166
- Cited by
- 60
- References
- 110
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 7 · 2018: 1 · 2017: 5 · 2016: 7 · 2015: 4 · 2014: 3 · 2013: 8 · 2012: 8
- FWCI
- 35.03
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Advances in experimental medicine and biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Richard and Susan Smith Family Foundation
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- glaucoma, synaptic pruning, retinal ganglion cell death, visual system development, reactive gliosis, neuroinflammation, neurodegeneration
- MeSH terms
- Animals, Complement Pathway, Classical, Disease Models, Animal, Glaucoma, Humans, Models, Neurological, Nerve Degeneration, Neuroglia, Retina, Retinal Ganglion Cells, Risk Factors, Synapses, Neuroimmunomodulation, Signal Transduction, Cell Death, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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