Mitchell Bradley M, Wu Tzu G, Chong Eva-Marie, Pate J Carey, Wilhelmus Kirk R
Sid W. Richardson Ocular Microbiology Laboratory, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA.
Cornea. 2007 Jun;26(5):589-93. doi: 10.1097/ICO.0b013e318033b504.
Levels of matrix metalloproteinases (MMPs) can be modulated during corneal infection, but little is known about MMP profiles during fungal keratitis. The purpose of this study was to determine the effect of corneal trauma and immunosuppressive treatment on the expression kinetics of MMP-2 and MMP-9 during experimental keratomycosis.
Corneas of immunocompetent and cyclophosphamide-treated adult BALB/c mice were topically inoculated with 1 x 10 culturable units of Fusarium solani or mock-inoculated with or without superficial corneal scarification. Eyes were scored daily for disease severity and processed for zymography after 1.5 hours, 6 hours, 1 day, 4 days, or 8 days. Gelatinase activity was densitometrically quantitated and normalized to MMP-2 and MMP-9 controls.
MMP-9 levels in nontraumatized eyes transiently increased at 6 hours after fungal exposure, but this increase was inhibited by cyclophosphamide treatment. Corneal injury significantly induced early MMP-9 expression that returned to baseline levels within 4 days. Cyclophosphamide pretreatment reduced and delayed MMP-9 after scarification. Fusarium exposure dampened the MMP-9 response to corneal trauma in immunocompetent and cyclophosphamide-treated animals. Ocular levels of MMP-2 were not affected by scarification, fungal exposure, or immunosuppressive treatment.
Ocular MMP-9 levels, but not MMP-2 levels, increased soon after corneal injury. A similar, although muted, MMP-9 response occurs during early filamentous fungal keratitis, with a kinetic profile similar to corneal disease progression. The early stage of ulcerative keratitis may involve selective regulation of corneal matrix metalloproteinases, suggesting an initial opportunity for therapeutic intervention.
基质金属蛋白酶（MMPs）水平在角膜感染期间可被调节，但对于真菌性角膜炎期间的MMP谱了解甚少。本研究的目的是确定角膜创伤和免疫抑制治疗对实验性角膜真菌病期间MMP-2和MMP-9表达动力学的影响。
将成年免疫活性和环磷酰胺处理的BALB/c小鼠的角膜局部接种1×10个可培养单位的茄病镰刀菌，或在有或无浅表角膜划痕的情况下进行模拟接种。每天对眼睛的疾病严重程度进行评分，并在1.5小时、6小时、1天、4天或8天后进行酶谱分析。通过光密度法对明胶酶活性进行定量，并以MMP-2和MMP-9对照进行标准化。
未受创伤的眼睛中，MMP-9水平在真菌暴露后6小时短暂升高，但这种升高被环磷酰胺治疗所抑制。角膜损伤显著诱导早期MMP-9表达，该表达在4天内恢复到基线水平。环磷酰胺预处理在划痕后降低并延迟了MMP-9的表达。在免疫活性和环磷酰胺处理的动物中，镰刀菌暴露减弱了对角膜创伤的MMP-9反应。MMP-2的眼内水平不受划痕、真菌暴露或免疫抑制治疗的影响。
角膜损伤后不久，眼内MMP-9水平升高，而MMP-2水平未受影响。在早期丝状真菌性角膜炎期间也会出现类似的MMP-9反应，尽管反应较弱，其动力学特征与角膜疾病进展相似。溃疡性角膜炎的早期阶段可能涉及角膜基质金属蛋白酶的选择性调节，这提示了治疗干预的初步机会。
