Purchase this article with an account.
Suzanne M J Fleiszig, Matteo Metruccio, Aaron Sullivan, Abby Kroken, Hart Horneman, Stephanie Wan, David J Evans; Contact lens wear can trigger clandestine parainflammation in mice.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):505.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Contact lens wear can cause various complications including sight-threatening corneal infection. Progress in understanding these problems has been handicapped by lack of in vivo models amenable to mouse-specific research tools. Here, we used custom-made silicone-hydrogel mouse contact lenses, reporter mice/fluorescent biomarkers, and high-resolution imaging, to study impact of lens-wear on corneal biology in vivo.
Murine contact lenses were fitted onto one eye of C57BL6/J-Rosa, CD11c-YFP, or Lyz2-GFP mice [labeling cell membrane-dTomato, dendritic cell-YFP or immune cells (lysozyme 2 expressing)-GFP respectively], or to MyD88 (-/-) or IL-1R (-/-) mice. Contralateral eyes were used as controls. In some experiments, lenses were inoculated with ~109 CFU/mL of P. aeruginosa PAO1 bacteria. Animals were monitored daily for up to 14 days. Eyes were imaged in vivo with a dissecting microscope, and also using live confocal imaging. Immunohistochemistry was then performed on corneal cryo-sections using NIMP-R14, a neutrophil-specific antibody. Image J and Imaris were used for 3D reconstruction, rendering and image analysis.
Control non-lens wearing corneas showed expected normal morphology with all methods used. In contrast, P. aeruginosa inoculated lens wear caused visible pathology in 10 of 29 mice, 3 infected after only 24 h. Lens wear without inoculation did not cause keratitis (0 of 25 mice), nor did it cause edema or surface irregularities notable using a dissecting microscope or histological sectioning. Live confocal imaging, however, revealed multiple differences from control non-lens wearing corneas. By 24 h, lens wear increased numbers of CD11c+ dendritic cells present in the central cornea (median 2.4 +/- 0.3-fold increase). Surprisingly, in 4/12 mice, highly motile Lyz2+ cells became visible, primarily in the stroma after 4 or more days of wear. Immunohistochemistry of these corneas revealed neutrophils in otherwise normal appearing stroma, a phenomenon absent without lens wear or in lens wearing MyD88 (-/-) and IL-1R (-/-) mice.
Contact lens wear alone can cause clandestine parainflammation in the cornea of mice, with recruitment of dendritic cells and neutrophils dependent on IL-1R and MyD88. The significance of this phenomenon in maintenance of corneal health during lens wear, and its contribution to pathology when pathogenic bacteria are also present, remain to be determined.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
This PDF is available to Subscribers Only