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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2016

Open Access 01-12-2016 | Research article

Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma

Authors: Pete A. Williams, James R. Tribble, Keating W. Pepper, Stephen D. Cross, B Paul Morgan, James E. Morgan, Simon W. M. John, Gareth R. Howell

Published in: Molecular Neurodegeneration | Issue 1/2016

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Abstract

Background

Glaucoma is a complex, multifactorial disease characterised by the loss of retinal ganglion cells and their axons leading to a decrease in visual function. The earliest events that damage retinal ganglion cells in glaucoma are currently unknown. Retinal ganglion cell death appears to be compartmentalised, with soma, dendrite and axon changes potentially occurring through different mechanisms. There is mounting evidence from other neurodegenerative diseases suggesting that neuronal dendrites undergo a prolonged period of atrophy, including the pruning of synapses, prior to cell loss. In addition, recent evidence has shown the role of the complement cascade in synaptic pruning in glaucoma and other diseases.

Results

Using a genetic (DBA/2J mouse) and an inducible (rat microbead) model of glaucoma we first demonstrate that there is loss of retinal ganglion cell synapses and dendrites at time points that precede axon or soma loss. We next determine the role of complement component 1 (C1) in early synaptic loss and dendritic atrophy during glaucoma. Using a genetic knockout of C1qa (D2.C1qa -/- mouse) or pharmacological inhibition of C1 (in the rat bead model) we show that inhibition of C1 is sufficient to preserve dendritic and synaptic architecture.

Conclusions

This study further supports assessing the potential for complement-modulating therapeutics for the prevention of retinal ganglion cell degeneration in glaucoma.
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Metadata
Title
Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma
Authors
Pete A. Williams
James R. Tribble
Keating W. Pepper
Stephen D. Cross
B Paul Morgan
James E. Morgan
Simon W. M. John
Gareth R. Howell
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2016
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-016-0091-6

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