The complement system is a major component of innate immunity and acts in parallel or in concert with the immune system. Complement activation provides an effective host defense mechanism against foreign organisms by generating effector molecules, which are involved in cell death and immune/inflammatory responses. Because of its potent inflammatory and destructive capabilities several complement regulatory proteins strictly control complement activation. These proteins provide a recognition system to distinguish self from non-self, thus limiting damage to host tissue. The anterior chamber of the eye is an immune privileged site and control of complement activation at this site may be important in preserving vision. Our results demonstrate that four complement regulatory proteins namely Crry, CD59, MCP and DAF are expressed within the normal rat eye and their expression is upregulated during experimental autoimmune anterior uveitis (EAAU). Furthermore, normal human intraocular fluid also contains a yet unidentified 55 kDa complement inhibitory protein. These results provide evidence that a complement regulatory system exists in the eye to protect ocular tissue from destruction by complement activating events. Identification and characterization of complement regulatory proteins in the eye would be a major advance toward the understanding of intraocular inflammation and protection of the eye. These studies should provide insights into the relevance of complement regulatory proteins in uveitis and may be therapeutically useful for suppressing intraocular inflammatory responses and tissue damage. The specific aims of this proposal are:

1. Role of complement regulatory proteins in experimental autoimmnune anterior uveitis (EAAU),

2. Suppression of EAAU by soluble complement regulatory protein(s), and

3. Characterization of 55 kDa complement inhibitor present in normal human aqueous humor/vitreous.

R01EY013335

2001-08-01

2007-07-31