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

• Published in: International journal of molecular sciences Vol. 22; no. 16; p. 8979
• Main Authors: Nishida, Teruo, Sugioka, Koji, Fukuda, Ken, Murakami, Junko
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 20.08.2021; MDPI
• Subjects: Antiinfectives and antibacterials; Antimicrobial agents; Bacteria; bacterial keratitis; Biodegradation; Blindness; Cell activation; Chemokines; Collagen; collagen degradation; Conversion; Cornea; corneal fibroblast; corneal ulcer; Cytokines; Cytotoxicity; Drug resistance; Epidemiology; Fibroblasts; Gram-negative bacteria; Gram-positive bacteria; Health services; Intercellular adhesion molecule 1; Interleukin 1; Interleukin 8; Keratitis; Leukocytes (neutrophilic); Leukocytes (polymorphonuclear); Matrix metalloproteinase; Matrix metalloproteinases; Medical treatment; Metalloproteinase; Microorganisms; Pathogens; Plasmin; Proteins; Pseudomonas aeruginosa; Review; Staphylococcus aureus; Stroma; Tumor necrosis factor-TNF; U-Plasminogen activator; Ulcers; Urokinase
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22168979

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.