The complement system is not only a fundamental element of our normal host defense against infection but is also involved in autoimmune tissue damage. It is a prime mediator of tissue inflammation. The present grant proposal is focused on the complement system and the role it plays in ocular inflammation.
Our specific aims for this grant period include the following: 1) Studies of complement in scleral tissue. Because there are no studies of complement in scleral tissue, we plan to demonstrate and quantitate antigenic levels of Clq, C3, C4, C5 and factor B in scleral eluates using single radial immunodiffusion. We also plan to demonstrate that scleral complement is functional by measuring levels of C1, C4, C2, C3, C5, C6 and C7 in scleral eluates using 50% hemolysis of sensitized red blood cells. We will also determine if molecular weight is an important factor in determining the concentration of complement components in the sclera and if there is more complement in the anterior than posterior sclera making it a more fertile tissue for immune reactions involving complement activation. 2) Effect of systemic decomplementation with cobra venom factor on corneal complement. We will determine whether short-term systemic decomplementation with cobra venom factor can substantially alter hemolytic complement levels in corneas and permit studies of the role of complement in corneal inflammation and infection. 3) Studies of activated complement fragments and leukotriene B4 in inflamed human aqueous humor and vitreous humor. Using the extremely sensitive technique of radioimmunoassay to measure levels of C3a, C4a, C5a and leukotriene B4, we will continue our studies in aqueous humor and extend them to vitreous humor where these inflammatory factors have never been identified before. We will attempt to correlate levels of these inflammatory mediators with different degrees and types of anterior and posterior segment inflammation. 4) In vitro studies of activated complement and leukotriene B4 in acute injuries of human corneas and sclera. We will try to determine if levels of activated complement and leukotriene B4 correlate with various acute injuries of the human cornea including alkali and acid burns, thermal and freezing injuries or injections of various inflammatory substances such as endotoxin. 5) Role of complement in host defense against gram-positive bacterial endophthalmitis. Little is known about host defense against bacterial endophthalmitis, a devastating and destructive disease. Using systemic decomplementation with cobra venom factor, we will try to determine if the complement system exerts a protective effect in host defense against gram-positive bacterial endophthalmitis.
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