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B. D. Novosad, R. Ramadan, J. Thurman, M. Callegan; Role of Toll-Like Receptors in Inflammation and Vision Loss During Bacillus Endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):496. doi: https://doi.org/.
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In the immune-privileged environment of the eye, the ability to effectively mount an inflammatory response to infection is determined by the ability to first recognize the offending pathogen. For Bacillus cereus endophthalmitis, the inflammatory response is explosive and vision loss is rapid. This study analyzed the role of toll-like receptors (TLR) 2 and 4 in the inflammatory response and resulting loss of vision during experimental Bacillus cereus endophthalmitis in the mouse.
C57BL6/J (wild type), homozygous TLR2-/-, or homozygous TLR4-/- knockout mice were injected into the midvitreous with 100 colony forming units (cfu) of B. cereus. Infections were analyzed by quantifying bacterial growth and infiltration of inflammatory cells (myeloperoxidase assay), analyzing retinal function by electroretinogram, and gross assessment of infection by histology and biomicroscopy (N≥4 eyes per assay per time point, mean ± SEM).
Growth of B. cereus was similar in eyes of wild type, TLR2-/-, and TLR4-/- knockout mice. However, inflammation in eyes of TLR2-/- and TLR4-/- knockout mice was delayed compared to that of eyes of wild type mice. The initial response in TLR2-/- and TLR4-/- knockout eyes was one of albumin infiltration only. PMN infiltration into wild type eyes began at 4 h, but inflammatory cells did not infiltrate into TLR2-/- or TLR4-/- mouse eyes until approximately 12 h postinfection. Retinal function declines in TLR2-/- and TLR4-/- mice were slower than that of wild type mice. By 12 h, A-wave amplitudes decreased in eyes of knockout mice, but lagged behind B-wave amplitude reductions, as is typically seen in this model. Retinas were essentially intact in TLR2-/- and TLR4-/- mouse eyes at 12 h, while retinas in eyes of wild type mice were completely destroyed.
These results suggested that the initial intraocular inflammatory response to B. cereus endophthalmitis was altered by silencing TLR2 or TLR4. Inflammation was not completely abrogated in TLR knockout mice, suggesting additional factors involved in bacterial recognition in the absence of these TLRs. Future studies will involve determining the bacterial ligands responsible for intraocular TLR recognition and the cells involved in the initial recognition response during bacterial endophthalmitis.
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