Aging, But Not Sex and Genetic Diversity, Impacts the Pathobiology of Bacterial Endophthalmitis
| Autor: | Sukhvinder Singh, Ashok Kumar, Ramandeep Rattan, Robert Emery Wright, Pawan Kumar Singh |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine retina H&E stain Enzyme-Linked Immunosorbent Assay diversity outbred Real-Time Polymerase Chain Reaction medicine.disease_cause Flow cytometry Pathogenesis Mice 03 medical and health sciences Sex Factors 0302 clinical medicine Endophthalmitis Electroretinography medicine Animals Immunology and Microbiology Innate immune system medicine.diagnostic_test business.industry aging Age Factors Genetic Variation Staphylococcal Infections S. aureus Flow Cytometry medicine.disease J:DO Mice Inbred C57BL female 030104 developmental biology inflammation Staphylococcus aureus ERG Immunology 030221 ophthalmology & optometry Increased inflammatory response business |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 |
| DOI: | 10.1167/iovs.61.14.5 |
| Popis: | Purpose Age, sex, and genetics are important biological variables in determining an individual's susceptibility or response to infectious agents; however, their role has not been evaluated in intraocular infections. In this study, we comprehensively examined the impact of these host biological factors in the pathogenesis of experimental bacterial endophthalmitis. Methods Endophthalmitis was induced by intravitreal injection of bacteria (Staphylococcus aureus) in the eyes of male and female C57BL/6 mice of different ages: group I (young, 6-8 weeks), group II (mid-age, 18-20 weeks), and group III (old, 1 year). Highly heterogeneous outbred J:DO mice were used for genetic diversity analysis. Eyes were subjected to clinical examination, retinal function testing using electroretinography (ERG), histopathological analysis (hematoxylin and eosin staining), and bacterial burden estimation. The levels of inflammatory mediators were measured using qPCR and ELISA, and the infiltration of neutrophils was determined by flow cytometry. Results Both inbred C57BL/6 and diversity outbred (J:DO) mice were equally susceptible to S. aureus endophthalmitis, as evidenced by a time-dependent increase in clinical scores, bacterial burden, intraocular inflammation, and retinal tissue damage, in addition to decreased retinal function. However, no significant differences were observed in disease severity and innate responses in male versus female mice. Older mice (group III) exhibited higher clinical scores coinciding with increased bacterial proliferation and intraocular inflammation, resulting in enhanced disease severity. Moreover, bone-marrow-derived macrophages from old mice exhibited reduced phagocytic activity but increased inflammatory response toward S. aureus challenge. Conclusions Age, but not sex, is an important biological variable in bacterial endophthalmitis. Identification of pathways underlying altered innate immunity and impaired bacterial clearance in aging eyes could provide new insights into the pathobiology of intraocular infections in elderly patients. |
| Databáze: | OpenAIRE |
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