Monitoring of Strain-Dependent Responsiveness to TLR Activation in the Mouse Anterior Segment Using SD-OCT

Abstract

Spectral-domain OCT enables high-resolution, longitudinal, in vivo imaging of anterior segment inflammation in mice and revealed novel strain- and time-dependent differences in response to distinct TLR activation in the cornea.

Longitudinal Changes to Tight Junction Expression and Endothelial Cell Integrity in a Mouse Model of Sterile Corneal Inflammation

“…6 Following the central corneal abrasion, 20 lg of phosphorothioate CpG 1826 (type B, TLR-9 ligand; Invivogen, San Diego, CA, USA) or sterile saline was applied to each eye. Animals were euthanized at 24 hours, 1 week and 4 weeks after treatment by lethal injection of sodium pentobarbitone (Lethabarb; Virbac Pty Ltd., Milperra, NSW, Australia).…”

“…Epithelial and stromal thicknesses were also quantified. A central image frame was determined, as we have previously described, 6 and CCT was taken as the mean measure from 11 frames, being the central image frame, five adjacent superior and inferior image frames.…”

“…6 In the present study, we included a later time point to examine whether the resolution of corneal edema at 1 week marked the end of the inflammatory response. Representative central anterior segment SD-OCT scans are shown 4 weeks after topical application of saline ( Fig.…”

“…Furthermore, corneal endothelial integrity can be assessed indirectly by monitoring corneal edema in mice using spectral-domain optical coherence tomography (SD-OCT). 6 Breakdown in endothelial tight junctions is associated with impaired ability of the cornea to control fluid uptake from the anterior chamber, leading to corneal edema and compromised light transmittance. 7 Epithelial stress, including hypoxia, is associated with aberrant expression of tight junctions between endothelial cells.…”

“…Application of TLR-9 ligand CpG-oligodeoxynucleotide (ODN) to the injured mouse cornea induces an acute phase of neutrophil and macrophage infiltration and corneal edema 6,11,12 followed by a later accumulation of giant macrophages in the stroma and keratic precipitates on the corneal endothelium. 13 The accumulation of keratic precipitates is not associated with overt structural changes to the corneal endothelium, and corneal edema largely subsides by 1 week, iovs.arvojournals.org j ISSN: suggesting that the presence of inflammatory cells in the cornea is not associated with corneal endothelial dysfunction.…”