The role of the classical complement cascade in synapse loss during development and glaucoma

Area of Science:

• Ophthalmology
• Neuroscience
• Immunology

Background:

• Glaucoma is a leading cause of global vision loss.
• The precise triggers for optic nerve axon degeneration and retinal ganglion neuron (RGC) loss in glaucoma are not fully understood.
• Early glaucoma stages involve reactive gliosis, inflammatory cytokines, and complement system activation.

Purpose of the Study:

• To review evidence supporting the
• synaptic
• hypothesis for glaucoma pathogenesis.
• To contextualize the role of the complement cascade within other known neurodegenerative mechanisms in glaucoma.

Main Methods:

• Review of current scientific literature.
• Analysis of evidence implicating the classical complement cascade in synaptic processes.
• Comparison of developmental synapse elimination with glaucoma-associated neurodegeneration.

Main Results:

• The classical complement cascade plays a role in eliminating excess synapses during development.
• Evidence suggests this developmental mechanism may be abnormally reactivated in glaucoma.
• Complement activation is observed in early stages of glaucoma models.

Conclusions:

• The "synaptic" hypothesis offers a potential explanation for early RGC loss in glaucoma.
• Complement-mediated synaptic elimination could be a key driver of glaucomatous neurodegeneration.
• Understanding these mechanisms is crucial for developing novel glaucoma therapies.