Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, Michigan, United States.
Division of Gynecology Oncology, Department of Women's Health Services, Henry Ford Health System, Detroit, Michigan, United States.
Invest Ophthalmol Vis Sci. 2020 Dec 1;61(14):5. doi: 10.1167/iovs.61.14.5.
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.
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.
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.
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.
年龄、性别和遗传是决定个体对感染因子易感性或反应的重要生物学变量；然而，它们在眼内感染中的作用尚未得到评估。在这项研究中，我们全面研究了这些宿主生物学因素在实验性细菌性眼内炎发病机制中的作用。
通过向不同年龄的雄性和雌性 C57BL/6 小鼠眼内注射细菌（金黄色葡萄球菌）诱导眼内炎：I 组（年轻，6-8 周）、II 组（中年，18-20 周）和 III 组（老年，1 岁）。使用高度异质的远交 J:DO 小鼠进行遗传多样性分析。对眼睛进行临床检查、视网膜功能测试（视网膜电图，ERG）、组织病理学分析（苏木精和伊红染色）和细菌负荷估计。使用 qPCR 和 ELISA 测量炎症介质水平，并通过流式细胞术确定中性粒细胞的浸润。
无论是近交 C57BL/6 还是遗传多样性远交（J:DO）小鼠，对金黄色葡萄球菌眼内炎均具有同等易感性，表现为临床评分、细菌负荷、眼内炎症和视网膜组织损伤随时间增加，以及视网膜功能下降。然而，在雄性和雌性小鼠之间，疾病严重程度和先天反应没有显著差异。老年（III 组）小鼠表现出更高的临床评分，同时细菌增殖和眼内炎症增加，导致疾病严重程度增加。此外，老年小鼠骨髓来源的巨噬细胞吞噬活性降低，但对金黄色葡萄球菌的炎症反应增强。
年龄是细菌性眼内炎的一个重要生物学变量，但性别不是。确定衰老眼中先天免疫改变和细菌清除受损的途径，可以为老年患者眼内感染的病理生物学提供新的见解。
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