Simultaneous Complement Response via Lectin Pathway in Retina and Optic Nerve in an Experimental Autoimmune Glaucoma...

Area of Science:

• Immunology
• Neuroscience
• Ophthalmology

Background:

• Glaucoma pathogenesis involves multifactorial mechanisms, including immune system contributions.
• Intraocular pressure-independent mechanisms and the complement system's role in glaucoma are not fully understood.
• Previous studies identified IgG deposits and retinal ganglion cell (RGC) loss in an autoimmune glaucoma model.

Purpose of the Study:

• To investigate the complement system's participation in an IOP-independent autoimmune glaucoma model.
• To determine if complement activation occurs early in the disease process.
• To explore the role of the lectin pathway in this glaucoma model.

Main Methods:

• Rats were immunized with bovine optic nerve homogenate antigen (ONA) or saline control.
• Quantification of RGC density using flatmounts.
• Immunohistochemical staining for complement components (C3, MAC) and myelin basic protein (MBP).
• Western blot and quantitative real-time PCR for complement factors (C3, MASP2).

Main Results:

• Significantly increased C3 and MAC depositions in retinas and optic nerves of ONA-immunized rats by day 7.
• Early upregulation of C3 protein and mRNA, and MASP2 in retinas and optic nerves.
• Complement activation preceded RGC loss and demyelination.
• No significant changes in C1q levels were observed.

Conclusions:

• Immunization triggers early complement system activation via the lectin pathway in retinas and optic nerves.
• This early complement activation is a potential trigger for subsequent degeneration in this glaucoma model.
• Findings suggest novel therapeutic strategies targeting the complement system for glaucoma treatment.