Roles of CCL2 and CCL3 in intraocular inflammation during Bacillus endophthalmitis

Abstract

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.