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Rachel L. Redfern, William J. Farley, Nimesh Patel, Samuel Hanlon, Stephen C. Pflugfelder, Alison McDermott; Dry Eye Mice are Resistant to Toll-Like Receptor Induced Inflammation. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3778.
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Dry eye is a multifactorial inflammatory disease that can increase the risk for corneal infection. Previously we have found that toll-like receptors (TLR) are upregulated in the mouse cornea, conjunctiva and lacrimal gland with experimental dry eye (EDE). This study examined if a TLR agonist cocktail applied onto the ocular surface increases risk for inflammation in mice with EDE or stimulates the production of antimicrobial peptides.
10-12 week old C57Bl/6 mice were subjected to a corneal scratch (n=3) or EDE (n=8) by subcutaneous scopolamine injection (2.5 mg/ml) four times a day and exposure to low humidity and an air draft for 5 days. 5µl of either TLR2, 3, 5 and 9 agonist cocktail or vehicle control was applied to the right or left eye respectively. HRT III and Spectralis OCT in vivo imaging was performed 24 hours later to examine the recruitment of inflammatory cells into the corneal stroma and to examine corneal fluorescein staining, central corneal thickness (CCT) and integrity. Eyes from mice with EDE were immunostained for mouse β-defensin (mBD)-3, mBD-4 or cathelin-related antimicrobial peptide (CRAMP).
TLR agonists significantly increased inflammatory cell recruitment into the corneal stroma in mice with a scratched cornea, but not in untreated (UT) or EDE mice. TLR agonists significantly increased the CCT in mice with a corneal scratch (165.6 ± 13.8µm vs. 122.3 ± 6.1µm) but significantly decreased CCT in EDE (87.15 ± 12.0µm vs. 114.1 ± 10.3 µm) compared to the vehicle control. UT mice had significantly less corneal staining than EDE mice. Central epithelial defects were detected in mice with EDE and were more common (75% vs 25% of animals) in TLR agonist treated eyes. TLR agonist treatment had no effect on mBD-3 or CRAMP but decreased corneal epithelial expression of mBD-4 in mice with EDE.
Mice with EDE are resistant to TLR induced corneal inflammation, but may be more susceptible to subsequent corneal infections due to epithelial defects and a decrease in mBD-4.
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