Experimental Pseudomonas aeruginosa Infection of the Mouse Cornea

Abstract

Pseudomonas aeruginosa infection of human cornea is rare but serious. The work of previous investigators using experimental infection primarily of rabbit cornea resulted in successful therapy for 10 to 50% of clinical cases. The advantage of using the mouse is demonstrated. The methods we adapted for characterizing the untreated experimental infection included: incising the cornea to enable establishing the infection; corneal examination with a steroscopic microscope; grading corneal pathology; qualitative and quantitative monitoring of the infecting bacteria by culturing and staining sectioned and dissected tissues. The characteristics of the tissue pathology, host response, and infection were similar to those reported for other animals and man. Corneal pathology was frequently nearly maximal 1 day after infection; host response involved a progression of events of long duration; pathology persisted well beyond the period of bacterial infection. The infection was essentially noncommunicable, and invasiveness was limited to the tissues of the incised eye. The results show the possibility of tests for invasiveness of clinical isolates and for screening for therapeutic and prophylactic measures.

Expression of Interleukin-6 in the Cornea in Response to Infection with Different Strains ofPseudomonas aeruginosa

“…The infiltrating cells in the cornea were confirmed histologically by hematoxylin-eosin staining as predominantly neutrophils (Fig. 1M, inset), in agreement with the observations of others (13, 14). Image analysis of sections probed for IL-6 mRNA showed that both the number and the intensity of cells staining positively for IL-6 mRNA increased during the course of the experiment (Fig.…”

Expression of Interleukin-6 in the Cornea in Response to Infection with Different Strains ofPseudomonas aeruginosa

“…The infiltrating cells in the cornea were confirmed histologically by hematoxylin-eosin staining as predominantly neutrophils (Fig. 1M, inset), in agreement with the observations of others (13, 14). Image analysis of sections probed for IL-6 mRNA showed that both the number and the intensity of cells staining positively for IL-6 mRNA increased during the course of the experiment (Fig.…”

Pseudomonas aeruginosa-mediated cytotoxicity and invasion correlate with distinct genotypes at the loci encoding exoenzyme S

“…The general trend for an increase over time in adherence by cytotoxic strains may be explained by the predilection of P. aeruginosa to bind to injured tissue. This property has been observed in other studies where injury to the cornea (6,9,22) or trachea (21,23) is required to initiate infection. It is unclear why PAO1 demonstrates the opposite pattern of an increase in association when the cytotoxicity pathway is rendered nonfunctional (as by an exsA mutation).…”

Age-Related Susceptibility to Pseudomonas aeruginosa Ocular Infections in Mice

“…The response of 21-day-old mice, on the other hand, was variable, with most animals (38%) exhibiting microphthalmia and cataracts, 30% undergoing phthisis bulbi, and 32% resolving the infection, presenting clear corneas within 3 to 4 weeks after infection. This broad range of responses, as well as the absence of microphthalmia and cataracts in 15-to 16-day-old animals, suggests a period of transition from total susceptibility to the organism, as observed in younger mice, to total resistance (with recovery of a clear cornea) to pseudomonas, as reported for adult animals (4,6,20). Adult (30-to 42postnatal-day Swiss-Webster) mice recover spontaneously from corneal wounding and topical administration of the organism and never exhibit systemic infection or death.…”

Expression of Interleukin-6 in the Cornea in Response to Infection with Different Strains ofPseudomonas aeruginosa

“…The infiltrating cells in the cornea were confirmed histologically by hematoxylin-eosin staining as predominantly neutrophils (Fig. 1M, inset), in agreement with the observations of others (13, 14). Image analysis of sections probed for IL-6 mRNA showed that both the number and the intensity of cells staining positively for IL-6 mRNA increased during the course of the experiment (Fig.…”

Pseudomonas aeruginosa-mediated cytotoxicity and invasion correlate with distinct genotypes at the loci encoding exoenzyme S

“…The general trend for an increase over time in adherence by cytotoxic strains may be explained by the predilection of P. aeruginosa to bind to injured tissue. This property has been observed in other studies where injury to the cornea (6,9,22) or trachea (21,23) is required to initiate infection. It is unclear why PAO1 demonstrates the opposite pattern of an increase in association when the cytotoxicity pathway is rendered nonfunctional (as by an exsA mutation).…”

Age-Related Susceptibility to Pseudomonas aeruginosa Ocular Infections in Mice

“…The response of 21-day-old mice, on the other hand, was variable, with most animals (38%) exhibiting microphthalmia and cataracts, 30% undergoing phthisis bulbi, and 32% resolving the infection, presenting clear corneas within 3 to 4 weeks after infection. This broad range of responses, as well as the absence of microphthalmia and cataracts in 15-to 16-day-old animals, suggests a period of transition from total susceptibility to the organism, as observed in younger mice, to total resistance (with recovery of a clear cornea) to pseudomonas, as reported for adult animals (4,6,20). Adult (30-to 42postnatal-day Swiss-Webster) mice recover spontaneously from corneal wounding and topical administration of the organism and never exhibit systemic infection or death.…”

Expression of Interleukin-6 in the Cornea in Response to Infection with Different Strains ofPseudomonas aeruginosa

“…The infiltrating cells in the cornea were confirmed histologically by hematoxylin-eosin staining as predominantly neutrophils (Fig. 1M, inset), in agreement with the observations of others (13, 14). Image analysis of sections probed for IL-6 mRNA showed that both the number and the intensity of cells staining positively for IL-6 mRNA increased during the course of the experiment (Fig.…”

Pseudomonas aeruginosa-mediated cytotoxicity and invasion correlate with distinct genotypes at the loci encoding exoenzyme S

“…The general trend for an increase over time in adherence by cytotoxic strains may be explained by the predilection of P. aeruginosa to bind to injured tissue. This property has been observed in other studies where injury to the cornea (6,9,22) or trachea (21,23) is required to initiate infection. It is unclear why PAO1 demonstrates the opposite pattern of an increase in association when the cytotoxicity pathway is rendered nonfunctional (as by an exsA mutation).…”

Age-Related Susceptibility to Pseudomonas aeruginosa Ocular Infections in Mice

“…The response of 21-day-old mice, on the other hand, was variable, with most animals (38%) exhibiting microphthalmia and cataracts, 30% undergoing phthisis bulbi, and 32% resolving the infection, presenting clear corneas within 3 to 4 weeks after infection. This broad range of responses, as well as the absence of microphthalmia and cataracts in 15-to 16-day-old animals, suggests a period of transition from total susceptibility to the organism, as observed in younger mice, to total resistance (with recovery of a clear cornea) to pseudomonas, as reported for adult animals (4,6,20). Adult (30-to 42postnatal-day Swiss-Webster) mice recover spontaneously from corneal wounding and topical administration of the organism and never exhibit systemic infection or death.…”