Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center; Department of Ophthalmology, Dean McGee Eye Institute.
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center.
J Vis Exp. 2021 Feb 6(168). doi: 10.3791/61749.
Intraocular bacterial infections are a danger to the vision. Researchers use animal models to investigate the host and bacterial factors and immune response pathways associated with infection to identify viable therapeutic targets and to test drugs to prevent blindness. The intravitreal injection technique is used to inject organisms, drugs, or other substances directly into the vitreous cavity in the posterior segment of the eye. Here, we demonstrated this injection technique to initiate infection in the mouse eye and the technique of quantifying intraocular bacteria. Bacillus cereus was grown in brain heart infusion liquid media for 18 hours and resuspended to a concentration 100 colony forming units (CFU)/0.5 µL. A C57BL/6J mouse was anesthetized using a combination of ketamine and xylazine. Using a picoliter microinjector and glass capillary needles, 0.5 µL of the Bacillus suspension was injected into the mid vitreous of the mouse eye. The contralateral control eye was either injected with sterile media (surgical control) or was not injected (absolute control). At 10 hours post infection, mice were euthanized, and eyes were harvested using sterile surgical tweezers and placed into a tube containing 400 µL sterile PBS and 1 mm sterile glass beads. For ELISAs or myeloperoxidase assays, proteinase inhibitor was added to the tubes. For RNA extraction, the appropriate lysis buffer was added. Eyes were homogenized in a tissue homogenizer for 1-2 minutes. Homogenates were serially diluted 10-fold in PBS and track diluted onto agar plates. The remainder of the homogenates were stored at -80 °C for additional assays. Plates were incubated for 24 hours and CFU per eye was quantified. These techniques result in reproducible infections in mouse eyes and facilitate quantitation of viable bacteria, the host immune response, and omics of host and bacterial gene expression.
眼内细菌感染对视力构成威胁。研究人员使用动物模型来研究与感染相关的宿主和细菌因素以及免疫反应途径,以确定可行的治疗靶点,并测试预防失明的药物。玻璃体内注射技术用于将生物制剂、药物或其他物质直接注射到眼球后段的玻璃体腔中。在这里,我们展示了这种注射技术来启动小鼠眼中的感染,并展示了定量眼内细菌的技术。蜡状芽孢杆菌在脑心浸液液体培养基中生长 18 小时,然后重悬至浓度为 100 个菌落形成单位 (CFU)/0.5 µL。使用氯胺酮和甲苯噻嗪的混合物麻醉 C57BL/6J 小鼠。使用皮升微注射器和玻璃毛细管针,将 0.5 µL 的蜡状芽孢杆菌悬浮液注射到小鼠眼球的中部玻璃体中。对侧对照眼要么注射无菌介质(手术对照),要么不注射(绝对对照)。感染后 10 小时,处死小鼠,用无菌手术镊子采集眼球,并放入含有 400 µL 无菌 PBS 和 1 毫米无菌玻璃珠的管中。对于 ELISA 或髓过氧化物酶测定,向管中加入蛋白酶抑制剂。对于 RNA 提取,加入适当的裂解缓冲液。用组织匀浆器将眼睛匀浆 1-2 分钟。将匀浆物在 PBS 中连续稀释 10 倍,并在琼脂平板上进行跟踪稀释。其余匀浆物储存在-80°C 用于进一步检测。平板孵育 24 小时,并定量每只眼的 CFU。这些技术可在小鼠眼中产生可重复的感染,并有助于定量活菌、宿主免疫反应以及宿主和细菌基因表达的组学。