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Int. J. Mol. Sci. 2017, 18(9), 1831;

Corneal Fibroblasts as Sentinel Cells and Local Immune Modulators in Infectious Keratitis

Department of Ophthalmology, Kochi Medical School, Nankoku City 783-8505, Japan
Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube City, Yamaguchi 755-8505, Japan
Ohshima Eye Hospital, Fukuoka City 812-0036, Japan
Author to whom correspondence should be addressed.
Received: 31 July 2017 / Revised: 21 August 2017 / Accepted: 21 August 2017 / Published: 23 August 2017
(This article belongs to the Special Issue Lipopolysaccharides (LPSs))
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The cornea serves as a barrier to protect the eye against external insults including microbial pathogens and antigens. Bacterial infection of the cornea often results in corneal melting and scarring that can lead to severe visual impairment. Not only live bacteria but also their components such as lipopolysaccharide (LPS) of Gram-negative bacteria contribute to the development of inflammation and subsequent corneal damage in infectious keratitis. We describe the important role played by corneal stromal fibroblasts (activated keratocytes) as sentinel cells, immune modulators, and effector cells in infectious keratitis. Corneal fibroblasts sense bacterial infection through Toll-like receptor (TLR)–mediated detection of a complex of LPS with soluble cluster of differentiation 14 (CD14) and LPS binding protein present in tear fluid. The cells then initiate innate immune responses including the expression of chemokines and adhesion molecules that promote the recruitment of inflammatory cells necessary for elimination of the infecting bacteria. Infiltrated neutrophils are activated by corneal stromal collagen and release mediators that stimulate the production of pro–matrix metalloproteinases by corneal fibroblasts. Elastase produced by Pseudomonas aeruginosa (P. aeruginosa) activates these released metalloproteinases, resulting in the degradation of stromal collagen. The modulation of corneal fibroblast activation and of the interaction of these cells with inflammatory cells and bacteria is thus important to minimize corneal scarring during treatment of infectious keratitis. Pharmacological agents that are able to restrain such activities of corneal fibroblasts without allowing bacterial growth represent a potential novel treatment option for prevention of excessive scarring and tissue destruction in the cornea. View Full-Text
Keywords: fibroblast; keratocyte; cornea; lipopolysaccharide; bacteria; chemokine; adhesion molecule; collagen; tear fluid fibroblast; keratocyte; cornea; lipopolysaccharide; bacteria; chemokine; adhesion molecule; collagen; tear fluid

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Fukuda, K.; Ishida, W.; Fukushima, A.; Nishida, T. Corneal Fibroblasts as Sentinel Cells and Local Immune Modulators in Infectious Keratitis. Int. J. Mol. Sci. 2017, 18, 1831.

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