A New Topical Model of<i>Staphylococcus</i>Corneal Infection in the Mouse

Girgis, Dalia O.; Sloop, Gregory D.; Reed, J.M.; O’Callaghan, Richard J.

doi:10.1167/iovs.02-0656

Cited by 46 publications

(42 citation statements)

References 27 publications

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“…One unit of MPO activity was equivalent to approximately 2 ϫ 10 5 PMNs. †Data for young mice that are derived from Girgis et al 22 ; ‡data for aged mice that are derived from Girgis et al 19 Because of the severity of infection of the parent strain (8325-4) in aged mice, these infections were not allowed to progress beyond 3 days PI. *Time points for which data could not be collected.…”

Section: Discussionmentioning

confidence: 99%

“…19,22 To anesthetize the mice, a 1.5-mL volume of xylazine (100 mg/mL; Rompum; Miles Laboratories, Shawnee Mission, KS) was combined with 10 mL ketamine HCl (100 mg/mL; Ketaset; Bristol Laboratories, Syracuse, NY), diluted 1:4 with saline, and injected subcutaneously at a dose of 0.1 mL/20 g body weight. Each cornea was scarified with a 30.5-gauge needle by making four parallel incisions to the corneal surface that did not penetrate beyond the superficial stroma.…”

Section: Infection Of Micementioning

confidence: 99%

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Effects of Toxin Production in a Murine Model ofStaphylococcus aureusKeratitis

Girgis¹,

Sloop

Reed³

et al. 2005

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To investigate the corneal virulence of toxin-deficient mutants of Staphylococcus aureus in young and aged mice in a topical inoculation model of keratitis. METHODS. Corneas of young and aged A/J mice were scarified and topically inoculated with a log phase S. aureus parent strain (8325-4), an ␣-toxin-deficient mutant (DU1090), or an Agr-defective mutant (ISP546) deficient in production of multiple toxins or with purified ␣-toxin. Slit lamp examination (SLE) and histopathology were performed, and bacterial colony-forming units (CFU) and myeloperoxidase (MPO) activity were determined. RESULTS. The infection of young mice with the mutant strains demonstrated significantly lower SLE scores (P Յ 0.0001) and reduced histopathologic changes compared with infections with the parent bacterial strain. Either mutant strain of S. aureus produced SLE scores in aged mice through 9 days after infection (PI) that were significantly lower than those of aged mice similarly infected with the toxin-producing parent strain (P Յ 0.0001). Despite use of identical inocula, the CFU per eye were greater for the parent than the mutant strains from 1 to 5 days PI in the young mice (P Յ 0.0372) and from 1 to 3 days PI in the aged mice (P Յ 0.0018). MPO activities were at the maximum at day 1 PI and were similar overall for all infections. Administration of purified ␣-toxin caused greater gross and histopathologic changes in eyes of aged mice than in those of young mice. CONCLUSIONS. Bacterial toxins, and especially ␣-toxin, can mediate corneal disease in mice. Differences in severity of S. aureus keratitis in aged versus young mice correlates with their susceptibility to ␣-toxin. (Invest Ophthalmol Vis Sci.

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Section: Discussionmentioning

confidence: 99%

Section: Infection Of Micementioning

confidence: 99%

Effects of Toxin Production in a Murine Model ofStaphylococcus aureusKeratitis

Girgis¹,

Sloop

Reed³

et al. 2005

Invest. Ophthalmol. Vis. Sci.

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“…Whereas the rabbit eye remains an appropriate model for the investigation of therapies designed to target bacteria and bacterial virulence factors, the mouse model would give a better understanding of the effects that bacteria and their virulence factors have on the host immune system and would thus provide possible host targets for the refinement of therapies to treat these infections. Mouse models of Staphylococcus aureus keratitis have been established and have proven useful for the study of the host response to infection [20][21][22] . The mouse model of Pseudomonas aeruginosa has been studied extensively and has provided insight into the host innate and adaptive immune responses to keratitis infection [23] .…”

Section: Development Of a Streptococcus Pneumoniae Keratitis Model Inmentioning

confidence: 99%

Development of a <i>Streptococcus pneumoniae </i>Keratitis Model in Mice

Moore¹,

McCormick²,

Norcross³

et al. 2009

Ophthalmic Res

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Background:Streptococcus pneumoniae is a common cause of bacterial keratitis, and models to examine the ocular pathogenesis of this bacterium would aid in efforts to treat pneumococcal keratitis. The aim of this study was to establish a murine model of pneumococcal keratitis. Methods: The corneas of A/J, BALB/c or C57BL/6 mice were scratched and topically infected with a clinical strain of S. pneumoniae. Slitlamp examination (SLE), enumeration of bacteria in the corneas and histology were performed. Results: Bacteria were recovered from the eyes of A/J mice on postinfection (PI) days 1 [1.96 ± 0.61 log₁₀ colony-forming units (CFU)] and 3 (1.41 ± 0.71 log₁₀ CFU). SLE scores were significantly higher in the infected A/J mice as compared to the BALB/c or C57BL/6 mice on PI day 3 (p < 0.0001) and steadily increased over time, reaching a maximal value of 3.00 ± 0.35 on PI day 10. Histopathology revealed stromal edema and the influx of polymorphonuclear leukocytes on PI days 7 and 10, and corneal disruption on PI day 7. Conclusions:S. pneumoniae keratitis was established in A/J mice, but not BALB/c or C57BL/6 mice.

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“…Ocular disease was evaluated in the anesthetized mouse using a slit lamp biomicroscope as described previously (19). Pathology was scored on a scale of 0 to 5 as follows: 0, clear eye; 1, slight redness in the corners; 2, moderate redness and injection; 3, conjunctival and corneal injection with ciliary flush; 4, extensive injection, generally associated with some mucus; and 5, most extensive injection, associated with excess mucus.…”

Section: Methodsmentioning

confidence: 99%

A Novel 5-Lipoxygenase-Activating Protein Inhibitor, AM679, Reduces Inflammation in the Respiratory Syncytial Virus-Infected Mouse Eye

Musiyenko

Correa²,

Stock³

et al. 2009

Clin Vaccine Immunol

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Respiratory syncytial virus (RSV) is an important cause of viral respiratory disease in children, and RSV bronchiolitis has been associated with the development of asthma in childhood. RSV spreads from the eye and nose to the human respiratory tract. Correlative studies of humans and direct infection studies of BALB/c mice have established the eye as a significant pathway of entry of RSV to the lung. At the same time, RSV infection of the eye produces symptoms resembling allergic conjunctivitis. Cysteinyl leukotrienes (CysLTs) are known promoters of allergy and inflammation, and the first step in their biogenesis from arachidonic acid is catalyzed by 5-lipoxygenase (5-LO) in concert with the 5-LO-activating protein (FLAP). We have recently developed a novel compound, AM679, which is a topically applied and potent inhibitor of FLAP. Here we show with the BALB/c mouse eye RSV infection model that AM679 markedly reduced the RSV-driven ocular pathology as well as the synthesis of CysLTs in the eye. In addition, AM679 decreased the production of the Th2 cell cytokine interleukin-4 but did not increase the viral load in the eye or the lung. These results suggest that FLAP inhibitors may be therapeutic for RSV-driven eye disease and possibly other inflammatory eye indications. Respiratory syncytial virus (RSV) (family Paramyxoviridae)is an enveloped virus with a single-stranded negative-sense RNA genome of 15.2 kb (8). Human RSV is the leading worldwide viral agent of serious pediatric respiratory tract disease (11). In the United States, ϳ100,000 children under 1 year of age are hospitalized with severe RSV infection, and approximately 90% of all children have been infected one or more times by 2 years of age (11). There is no effective treatment for severe RSV infections, but with high-risk children the RSVneutralizing antibody palivizumab (Synagis) can be used to prevent the development of the disease (6). RSV bronchiolitis is associated with the development of wheezing symptoms and asthma in childhood, and RSV is also a significant cause of morbidity and mortality in the elderly and severely immunocompromised patients (11,12).Inoculation of RSV to the human nose or eyes results in viral replication, with an incubation period of 4 to 5 days, and the virus can then spread to the lower respiratory tract (8). This reflects the anatomical connection between the optic and nasal/upper respiratory tissues, and it is known that the use of eye goggles and nose masks significantly reduces RSV infection from patients to hospital workers (16). With BALB/c mice, instillation of RSV in the eye leads to eye infection, inflammation, and eye-to-lung viral transmission, resulting in respiratory pathology (3). In addition, many chemokines and receptors and interleukin 1␣ (IL-1␣) and tumor necrosis factor (TNF) were induced in the RSV-infected mouse eyes (3). In this study, application of anti-RSV small interfering RNA to the eyes 30 min prior to RSV inoculation prevented both viral growth and virus-induced pathology in the eye and lun...

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A New Topical Model ofStaphylococcusCorneal Infection in the Mouse

Cited by 46 publications

References 27 publications

Effects of Toxin Production in a Murine Model ofStaphylococcus aureusKeratitis

Effects of Toxin Production in a Murine Model ofStaphylococcus aureusKeratitis

Development of a <i>Streptococcus pneumoniae </i>Keratitis Model in Mice

A Novel 5-Lipoxygenase-Activating Protein Inhibitor, AM679, Reduces Inflammation in the Respiratory Syncytial Virus-Infected Mouse Eye

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