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.
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