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Review

Pivotal Role of Corneal Fibroblasts in Progression to Corneal Ulcer in Bacterial Keratitis

1
Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan
2
Division of Cornea and Ocular Surface, Ohshima Eye Hospital, Fukuoka 812-0036, Japan
3
Department of Ophthalmology, Kindai University Nara Hospital, Ikoma, Nara 630-0293, Japan
4
Department of Ophthalmology and Visual Science, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan
5
Division of Ophthalmology, Sakibana Hospital, Izumi, Osaka 594-1105, Japan
*
Author to whom correspondence should be addressed.
Academic Editors: Hang Thi Thu Nguyen, Jéremy Jéremy Denizot and Elisabeth Billard
Int. J. Mol. Sci. 2021, 22(16), 8979; https://doi.org/10.3390/ijms22168979
Received: 18 July 2021 / Revised: 12 August 2021 / Accepted: 17 August 2021 / Published: 20 August 2021
(This article belongs to the Special Issue Molecular Mechanisms of Host-Pathogen Interaction)
The shape and transparency of the cornea are essential for clear vision. However, its location at the ocular surface renders the cornea vulnerable to pathogenic microorganisms in the external environment. Pseudomonas aeruginosa and Staphylococcus aureus are two such microorganisms and are responsible for most cases of bacterial keratitis. The development of antimicrobial agents has allowed the successful treatment of bacterial keratitis if the infection is diagnosed promptly. However, no effective medical treatment is available after progression to corneal ulcer, which is characterized by excessive degradation of collagen in the corneal stroma and can lead to corneal perforation and corneal blindness. This collagen degradation is mediated by both infecting bacteria and corneal fibroblasts themselves, with a urokinase-type plasminogen activator (uPA)-plasmin-matrix metalloproteinase (MMP) cascade playing a central role in collagen destruction by the host cells. Bacterial factors stimulate the production by corneal fibroblasts of both uPA and pro-MMPs, released uPA mediates the conversion of plasminogen in the extracellular environment to plasmin, and plasmin mediates the conversion of secreted pro-MMPs to the active form of these enzymes, which then degrade stromal collagen. Bacterial factors also stimulate expression by corneal fibroblasts of the chemokine interleukin-8 and the adhesion molecule ICAM-1, both of which contribute to recruitment and activation of polymorphonuclear neutrophils, and these cells then further stimulate corneal fibroblasts via the secretion of interleukin-1. At this stage of the disease, bacteria are no longer necessary for collagen degradation. In this review, we discuss the pivotal role of corneal fibroblasts in corneal ulcer associated with infection by P. aeruginosa or S. aureus as well as the development of potential new modes of treatment for this condition. View Full-Text
Keywords: corneal fibroblast; corneal ulcer; bacterial keratitis; collagen degradation; Pseudomonas aeruginosa; Staphylococcus aureus; matrix metalloproteinase; polymorphonuclear neutrophil; cytokine corneal fibroblast; corneal ulcer; bacterial keratitis; collagen degradation; Pseudomonas aeruginosa; Staphylococcus aureus; matrix metalloproteinase; polymorphonuclear neutrophil; cytokine
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MDPI and ACS Style

Nishida, T.; Sugioka, K.; Fukuda, K.; Murakami, J. Pivotal Role of Corneal Fibroblasts in Progression to Corneal Ulcer in Bacterial Keratitis. Int. J. Mol. Sci. 2021, 22, 8979. https://doi.org/10.3390/ijms22168979

AMA Style

Nishida T, Sugioka K, Fukuda K, Murakami J. Pivotal Role of Corneal Fibroblasts in Progression to Corneal Ulcer in Bacterial Keratitis. International Journal of Molecular Sciences. 2021; 22(16):8979. https://doi.org/10.3390/ijms22168979

Chicago/Turabian Style

Nishida, Teruo, Koji Sugioka, Ken Fukuda, and Junko Murakami. 2021. "Pivotal Role of Corneal Fibroblasts in Progression to Corneal Ulcer in Bacterial Keratitis" International Journal of Molecular Sciences 22, no. 16: 8979. https://doi.org/10.3390/ijms22168979

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