Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Division of Cornea and Ocular Surface, Ohshima Eye Hospital, Fukuoka 812-0036, Japan.
Int J Mol Sci. 2021 Aug 20;22(16):8979. 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. and 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 or as well as the development of potential new modes of treatment for this condition.
角膜的形状和透明度对清晰的视力至关重要。然而，由于其位于眼表面，因此容易受到外部环境中致病微生物的影响。和是两种这样的微生物，是大多数细菌性角膜炎的罪魁祸首。如果感染能及时诊断，抗菌药物的发展使细菌性角膜炎的治疗成为可能。然而，如果进展为角膜溃疡，就没有有效的治疗方法，因为角膜溃疡会导致角膜基质中胶原的过度降解，并可能导致角膜穿孔和失明。这种胶原降解既由感染细菌介导，也由角膜成纤维细胞本身介导，尿激酶型纤溶酶原激活物（uPA）-纤溶酶-基质金属蛋白酶（MMP）级联反应在宿主细胞的胶原破坏中起着核心作用。细菌因素刺激角膜成纤维细胞产生 uPA 和 pro-MMPs，释放的 uPA 介导细胞外环境中纤溶酶原转化为纤溶酶，纤溶酶介导分泌的 pro-MMPs 转化为这些酶的活性形式，然后降解基质胶原。细菌因素还刺激角膜成纤维细胞表达趋化因子白细胞介素-8 和细胞间黏附分子-1，这两者都有助于招募和激活多形核中性粒细胞，这些细胞通过分泌白细胞介素-1进一步刺激角膜成纤维细胞。在疾病的这个阶段，细菌对于胶原降解不再是必需的。在这篇综述中，我们讨论了角膜成纤维细胞在与或感染相关的角膜溃疡中的关键作用，以及为这种情况开发新的潜在治疗模式。
