Deficiency of complement component 5 ameliorates glaucoma in DBA/2J mice.

Area of Science:

• Ophthalmology
• Neuroscience
• Immunology

Background:

• Glaucoma is an age-related neurodegenerative disease causing blindness through retinal ganglion cell (RGC) loss.
• Inflammatory processes, particularly complement cascade activation, are implicated early in glaucoma pathogenesis.
• DBA/2J mice, a glaucoma model, are naturally deficient in complement component 5 (C5), limiting studies on its role.

Purpose of the Study:

• To investigate the role of complement component 5 (C5) in the development and severity of glaucoma.
• To determine the impact of C5 restoration on glaucoma progression in DBA/2J mice.

Main Methods:

• A functional C5 gene was backcrossed into DBA/2J mice to create C5-sufficient models.
• Glaucoma was assessed via ocular exams, intraocular pressure (IOP) measurements, and optic nerve/RGC damage evaluation.
• C5 expression was analyzed in retinas and optic nerves using immunofluorescence.

Main Results:

• C5-sufficient DBA/2J mice exhibited more severe glaucoma at an earlier age compared to C5-deficient mice.
• Membrane attack complex components were detected at sites of optic nerve injury and RGCs.
• C5 deficiency confers protection against glaucoma progression in this model.

Conclusions:

• C5 plays a significant role in glaucoma pathogenesis, with deficiency mitigating disease severity.
• Understanding the complement cascade's role is crucial for neurodegenerative disease research.
• Targeting C5 inhibition presents a potential therapeutic strategy for human glaucoma.