Eye infections due to P. aeruginosa are particularly dangerous to those debilitated by age, to newborns, and to those who have experienced corneal abrasions or puncture due to industrial accidents. The overall purpose of this study is to use a multi-disciplinary approach (histological, microbiological, genetic, and immunological) to characterize the natural defense mechanism(s) of murine eyes to challenge with Pseudomonas aeruginosa. The presence or absence of natural resistance to infection will be studied in the following animal models: (a) naturally resistant mouse strains which mount an extensive PMN response and spontaneously recover from intracorneal-bacterial challenge within two to three weeks (Swiss-Webster, DBA/1, DBA/2, etc.); (b) susceptible strains which suffer irreversible destruction of the eye (BALB/c); and (c) the BALB/c-derived nude (nu/nu) mouse which is also resistant to intracorneal infection, but differs from the other resistant strains by the ability to clear the infection within 24 hrs with no apparent cellular infiltration (hyper-resistant). Characterization and quantitation of specific and non-specific factors present in naturally resistant mouse strains (and absent in susceptible strains) will be initiated. In addition, the various cellular and humoral factors that play a role in protecting immunized (initially susceptible) mice will be studied. Concomitantly, the varying responses of various susceptible and resistant inbred mouse strains, F1 and F2 hybrid progeny and various backcrosses to intracorneal challenge, will be genetically screened in order to determine the number and location of the genes regulating natural resistance.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY001935-08
Application #
3256348
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1977-08-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
Kernacki, K A; Fridman, R; Hazlett, L D et al. (1997) In vivo characterization of host and bacterial protease expression during Pseudomonas aeruginosa corneal infections in naive and immunized mice. Curr Eye Res 16:289-97
Kernacki, K A; Berk, R S (1995) Characterization of arachidonic acid metabolism and the polymorphonuclear leukocyte response in mice infected intracorneally with Pseudomonas aeruginosa. Invest Ophthalmol Vis Sci 36:16-23
Kernacki, K A; Hobden, J A; Hazlett, L D et al. (1995) In vivo bacterial protease production during Pseudomonas aeruginosa corneal infection. Invest Ophthalmol Vis Sci 36:1371-8
Kernacki, K A; Berk, R S (1994) Characterization of the inflammatory response induced by corneal infection with Pseudomonas aeruginosa. J Ocul Pharmacol 10:281-8
Rudner, X L; Berk, R S; Hazlett, L D (1993) Immunization with homologous Pseudomonas aeruginosa pili protects against ocular disease. Reg Immunol 5:245-52
Preston, M J; Kernack, K; Berk, R S (1993) Kinetics of serum and ocular antibody responses in susceptible mice that received a secondary corneal infection with Pseudomonas aeruginosa. Infect Immun 61:2713-6
Meyers, D J; Palmer, K C; Bale, L A et al. (1992) In vivo and in vitro toxicity of phospholipase C from Pseudomonas aeruginosa. Toxicon 30:161-9
Hazlett, L D; Zucker, M; Berk, R S (1992) Distribution and kinetics of the inflammatory cell response to ocular challenge with Pseudomonas aeruginosa in susceptible versus resistant mice. Ophthalmic Res 24:32-9
Preston, M J; Kernacki, K A; Berk, J M et al. (1992) Kinetics of serum, tear, and corneal antibody responses in resistant and susceptible mice intracorneally infected with Pseudomonas aeruginosa. Infect Immun 60:885-91
Rudner, X L; Zheng, Z; Berk, R S et al. (1992) Corneal epithelial glycoproteins exhibit Pseudomonas aeruginosa pilus binding activity. Invest Ophthalmol Vis Sci 33:2185-93

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