Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Dean McGee Eye Institute, Oklahoma City, OK, USA.
Exp Eye Res. 2022 Nov;224:109213. doi: 10.1016/j.exer.2022.109213. Epub 2022 Sep 2.
Bacillus cereus (B. cereus) endophthalmitis is a vision-threatening bacterial infection. Uncontrolled inflammatory responses are the hallmark of this disease which cause irreversible damage to the retina. We recently reported C-X-C chemokines as a vital modulators which impacted the pathogenesis of this disease. Here, we investigated the impact of two highly upregulated C-C chemokines, CCL2 and CCL3, on intraocular inflammation this disease. B. cereus was injected into the eyes of C57BL/6J (WT), CCL2, and CCL3 mice to induce endophthalmitis. Infected eyes were examined for bacterial growth, retinal function, and inflammation. Bacterial growth in CCL2 and CCL3 mice were similar, but retained retinal function was greater in CCL2 and CCL3 eyes compared to that of C57BL/6J eyes. The retinal architecture of infected eyes of CCL2 mice were conserved for a longer period of time than in infected CCL3 eyes. Infected CCL2 and CCL3 eyes had less inflammation than did infected C57BL/6J eyes. Based on these results, we assessed the efficacies of intravitreal anti-CCL2 or anti-CCL3 with or without the antibiotic gatifloxacin. Compared to infected untreated eyes, there was significantly less inflammation and greater retention of retinal function in eyes treated with anti-CCL2 or anti-CCL3 with gatifloxacin. This study showed that B. cereus endophthalmitis in CCL2 mice had a better clinical outcome than in CCL3 mice. Intravitreal administration of anti-CCL2 and anti-CCL3 with gatifloxacin significantly reduced inflammation and provided protection of retinal function. These results suggest that CCL2 and CCL3 are prospective anti-inflammatory targets that should be tested along with other antibiotics for treating Bacillus and perhaps other forms of endophthalmitis.
蜡样芽胞杆菌(B. cereus)眼内炎是一种威胁视力的细菌性感染。不受控制的炎症反应是这种疾病的标志,它会导致视网膜不可逆转的损伤。我们最近报道 C-X-C 趋化因子作为一种重要的调节剂,影响这种疾病的发病机制。在这里,我们研究了两种高度上调的 C-C 趋化因子 CCL2 和 CCL3 对该疾病眼内炎症的影响。将蜡样芽胞杆菌注入 C57BL/6J(WT)、CCL2 和 CCL3 小鼠的眼睛中以诱导眼内炎。检查受感染眼睛的细菌生长、视网膜功能和炎症情况。CCL2 和 CCL3 小鼠中的细菌生长相似,但与 C57BL/6J 眼睛相比,CCL2 和 CCL3 眼睛保留的视网膜功能更大。CCL2 感染眼睛的视网膜结构在较长时间内保持不变,而 CCL3 感染眼睛则不是。与 C57BL/6J 感染眼睛相比,CCL2 和 CCL3 感染眼睛的炎症更少。基于这些结果,我们评估了玻璃体内注射抗 CCL2 或抗 CCL3 联合或不联合抗生素加替沙星的疗效。与未经处理的感染眼睛相比,用抗 CCL2 或抗 CCL3 联合加替沙星治疗的眼睛炎症明显减少,视网膜功能保留更多。这项研究表明,与 CCL3 感染小鼠相比,CCL2 感染小鼠的蜡样芽胞杆菌眼内炎临床结局更好。玻璃体内注射抗 CCL2 和抗 CCL3 联合加替沙星可显著减轻炎症并保护视网膜功能。这些结果表明,CCL2 和 CCL3 是有前途的抗炎靶点,应与其他抗生素一起用于治疗芽孢杆菌和其他形式的眼内炎。