Roles of CCL2 and CCL3 in intraocular inflammation during Bacillus endophthalmitis

Md Huzzatul Mursalin; Roger Astley; Phillip S Coburn; Frederick C Miller; Michelle C Callegan

doi:10.1016/j.exer.2022.109213

Roles of CCL2 and CCL3 in intraocular inflammation during Bacillus endophthalmitis

Exp Eye Res. 2022 Nov:224:109213. doi: 10.1016/j.exer.2022.109213. Epub 2022 Sep 2.

Authors

Md Huzzatul Mursalin¹, Roger Astley², Phillip S Coburn², Frederick C Miller³, Michelle C Callegan⁴

Affiliations

¹ Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
² Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Dean McGee Eye Institute, Oklahoma City, OK, USA.
³ Department of Cell Biology and Department of Family and Preventive Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
⁴ Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Dean McGee Eye Institute, Oklahoma City, OK, USA; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: http://calleganlab.org.

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.

Keywords: Bacillus cereus; Chemokine; Endophthalmitis; Immune responses; Inflammation; Ocular infection.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Anti-Bacterial Agents / therapeutic use
Bacillus cereus
Bacillus*
Chemokine CCL2* / genetics
Chemokine CCL3 / genetics
Electroretinography
Endophthalmitis* / drug therapy
Endophthalmitis* / microbiology
Eye Infections, Bacterial* / drug therapy
Eye Infections, Bacterial* / microbiology
Gatifloxacin / therapeutic use
Inflammation
Mice
Mice, Inbred C57BL
Uveitis*

Substances

Anti-Bacterial Agents
Ccl3 protein, mouse
Chemokine CCL3
Gatifloxacin
Ccl2 protein, mouse
Chemokine CCL2

Abstract

Publication types

MeSH terms

Substances

Grants and funding