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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004607-09
Application #
3259077
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1982-05-01
Project End
1992-12-31
Budget Start
1990-01-01
Budget End
1990-12-31
Support Year
9
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Mondino, B J; Chou, H J; Sumner, H L (1996) Generation of complement membrane attack complex in normal human corneas. Invest Ophthalmol Vis Sci 37:1576-81
Gardner, B P; Pleyer, U; Mondino, B J et al. (1995) Complement-derived anaphylatoxins in human donor corneas treated with excimer laser. Ophthalmic Surg Lasers 26:568-71
Giese, M J; Mondino, B J; Glasgow, B J et al. (1994) Complement system and host defense against staphylococcal endophthalmitis. Invest Ophthalmol Vis Sci 35:1026-32
Milani, J K; Pleyer, U; Dukes, A et al. (1993) Prolongation of corneal allograft survival with liposome-encapsulated cyclosporine in the rat eye. Ophthalmology 100:890-6
Pleyer, U; Mondino, B J; Sumner, H L (1992) The effect of systemic decomplementation with cobra venom factor on corneal complement levels in guinea pigs. Invest Ophthalmol Vis Sci 33:2212-5
Harrison, S A; Mondino, B J; Mayer, F J (1990) Scleral fibroblasts. Human leukocyte antigen expression and complement production. Invest Ophthalmol Vis Sci 31:2412-9
Harrison, S A; Mondino, B J; Kagan, J M (1990) Modulation of HLA antigen expression on conjunctival fibroblasts by gamma-interferon. Invest Ophthalmol Vis Sci 31:163-7
Mondino, B J; Sidikaro, Y; Mayer, F J et al. (1990) Inflammatory mediators in the vitreous humor of AIDS patients with retinitis. Invest Ophthalmol Vis Sci 31:798-804
Dunn Jr, J P; Berger, S T; Mondino, B J et al. (1990) Ocular trauma caused by exploding glass bottles containing dry ice and water. Ophthalmic Surg 21:628-31
Mondino, B J; Sumner, H L (1990) Generation of complement-derived anaphylatoxins in normal human donor corneas. Invest Ophthalmol Vis Sci 31:1945-9

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