Chronic low level complement activation within the eye is controlled by intraocular complement regulatory proteins

Area of Science:

• Ophthalmology
• Immunology
• Complement System Biology

Background:

• The eye is an immune-privileged site, necessitating intricate regulatory mechanisms to maintain homeostasis.
• The complement system, a key part of innate immunity, plays a critical role in host defense but can also cause tissue damage if dysregulated.
• Understanding complement regulation within the eye is crucial for managing ocular inflammatory diseases.

Purpose of the Study:

• To investigate the expression and function of complement regulatory proteins within the eye.
• To elucidate the role of the complement system in ocular inflammation, specifically anterior uveitis.

Main Methods:

• Analysis of complement regulatory proteins (MCP, DAF, CD59, Crry) in rat eyes using immunohistochemistry, Western blot, and RT-PCR.
• Induction of anterior uveitis via intraocular injection of zymosan or anti-Crry/anti-CD59 antibodies in Lewis rats.
• Complement depletion using cobra venom factor (CVF) to assess its role in antibody-induced uveitis.

Main Results:

• Complement regulatory proteins (MCP, DAF, CD59, Crry) and membrane attack complex (MAC) are present in normal rat eyes.
• Intraocular zymosan injection induced severe anterior uveitis.
• Neutralizing anti-Crry antibodies triggered anterior uveitis with increased C3 split products, which was prevented by systemic complement depletion.
• Anti-CD59 antibodies did not induce inflammation.

Conclusions:

• The complement system is constitutively active at a low level in the normal eye.
• Intraocular complement regulatory proteins play a vital role in controlling complement-mediated inflammation.
• Crry is essential for regulating complement activation and preventing anterior uveitis in the rat eye model.