Although Staphylococcus aureus and epidermis are important and common bacterial causes of ocular disease, little is known about the ocular immune response to these organisms. In addition to destruction caused by proliferating S. aureus and its toxins, hypersensitivity to this organism may be associated with blepharitis and corneal phlyctenules and catarrhal infiltrates. Our rabbit models of staphylococcal endophthalmitis and hypersensitivity diseases have enabled us to study the immune response associated with these important diseases. This grant continues to focus on our animal models of human disease and has two major specific aims: (1) treatment of staphylococcal blepharitis and corneal hypersensitivity lesions using Staphage Lysate (SPL) and (2) the immune response to staphylococcal endophthalmitis in the rat. There is renewed interest in using SPL to treat resistant cases of staphylococcal blepharitis and corneal hypersensitivity lesions in humans. Before human studies, it would be reasonable to test SPL in our rabbit model to determine: (1) the effect of SPL injections on delayed-type hypersensitivity (DTH) to S. aureus (measured by skin tests) and antibody titers (measured by ELISA) in serum, tears and corneas of normal rabbits, (2) the effect of SPL on DTH and antibody titers in our rabbit model of staphylococcal blepharitis and corneal hypersensitivity lesions, and (3) the impact of SPL on the development and evolution of blepharitis and corneal hypersensitivity lesions. Except for our studies of S. aureus endophthalmitis and S. epidermis endophthalmitis in rabbits, there have been no reports examining the immune response to staphylococcal endophthalmitis or, for that matter, to any type of bacterial endophthalmitis which is a devastating disease in humans. Since the rat immune system is much better defined than the rabbit, we would like to pursue future studies in Lewis rats. Proposed studies are directed at both the systematic and ocular immune response to staphylococcal endophthalmitis and include: studies of cell- mediated immunity to staphylococcal antigens using skin tests for DTH and lymphocyte proliferation assays; studies of humoral immunity to staphylococcal antigens using an ELISA to measure antibody levels in blood; immunohistochemistry to characterize changes and orientation of lymphocyte phenotypes in lymph nodes and spleen cell sorting analysis to characterize changes in lymphocyte phenotypes in blood, lymph nodes spleen; and studies of the time course of development of endophthalmitis in the rat eye, using immunohistochemistry to characterize leukocytes infiltrating cytokine and antibody measurements in vitreous, and correlation of the immune response with clinical observations, culture results and gross and histopathologic findings. Athymic nude rat will allow us to determine the importance of T cells. These studies should enable us to characterize for the first time the immune response to staphylococcal endophthalmitis, the most important cause of postoperative bacterial endophthalmitis in humans.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004606-13
Application #
2159108
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1982-05-01
Project End
1996-04-30
Budget Start
1994-05-01
Budget End
1995-04-30
Support Year
13
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Giese, M J; Mondino, B J (2001) Experimental staphylococcal endophthalmitis. Ophthalmologica 215:321-36
Giese, M J; Shum, D C; Rayner, S A et al. (2000) Adhesion molecule expression in a rat model of Staphylococcus aureus endophthalmitis. Invest Ophthalmol Vis Sci 41:145-53
Yoshizumi, M O; Kashani, A; Palmer, J et al. (1999) High dose intramuscular methylprednisolone in experimental Staphylococcus aureus endophthalmitis. J Ocul Pharmacol Ther 15:91-6
Giese, M J; Berliner, J A; Riesner, A et al. (1999) A comparison of the early inflammatory effects of an agr-/sar- versus a wild type strain of Staphylococcus aureus in a rat model of endophthalmitis. Curr Eye Res 18:177-85
Giese, M J; Sumner, H L; Berliner, J A et al. (1998) Cytokine expression in a rat model of Staphylococcus aureus endophthalmitis. Invest Ophthalmol Vis Sci 39:2785-90
Yoshizumi, M O; Lee, G C; Equi, R A et al. (1998) Timing of dexamethasone treatment in experimental Staphylococcus aureus endophthalmitis. Retina 18:130-5
Ravindranath, R M; Hasan, S A; Mondino, B J (1997) Immunopathologic features of Staphylococcus epidermidis-induced endophthalmitis in the rat. Curr Eye Res 16:1036-43
Pleyer, U; Milani, J K; Ruckert, D et al. (1997) Determinations of serum tumor necrosis factor alpha in corneal allografts. Ocul Immunol Inflamm 5:149-55
Giese, M J; Adamu, S A; Pitchekian-Halabi, H et al. (1996) The effect of Staphylococcus aureus phage lysate vaccine on a rabbit model of staphylococcal blepharitis, phlyctenulosis, and catarrhal infiltrates. Am J Ophthalmol 122:245-54
Ravindranath, R M; Mondino, B J; Adamu, S A et al. (1995) Immunopathologic features of Staphylococcus aureus endophthalmitis in the rat. Invest Ophthalmol Vis Sci 36:2482-91

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