Wolf Marie, Maltseva Inna, Clay Selene M, Pan Peipei, Gajjala Abhinay, Chan Matilda F
Department of Ophthalmology, University of California, San Francisco, CA, United States.
Department of Anatomy, University of California, San Francisco, CA, United States.
Exp Eye Res. 2017 Jul;160:11-20. doi: 10.1016/j.exer.2017.04.007. Epub 2017 Apr 22.
Corneal epithelial defects are a common cause of ocular morbidity and can result in corneal scarring if they do not heal properly. Matrix metalloproteinases (MMPs) are extracellular matrix proteinases that regulate multiple aspects of corneal repair. We have previously shown that MMP12 has a protective effect on corneal fibrosis through its regulation of neutrophil and macrophage infiltration and angiogenesis in a chemical injury model involving full thickness damage to the cornea. However, the role of MMP12 in injuries limited to the corneal epithelium is relatively unknown. This study investigates the reparative effects of MMP12 following isolated corneal epithelial injury. Using a corneal epithelial debridement injury model performed on corneas of wild-type (WT) mice, we show that Mmp12 is expressed early following corneal epithelial injury with highest expression levels at 8 h after injury and lower expression levels at 4 and 8 days after injury. We investigated whether MMP12 has an effect on the rate of epithelial repair and cell migration using in vivo and in vitro scratch assays performed on WT and Mmp12 mice. We found that loss of MMP12 results in a slower scratch wound repair rate both in vivo and in vitro. We also found that corneas of Mmp12 mice have decreased neutrophil infiltration following injury. Loss of MMP12, however, does not affect cell proliferation in the center of the wounds. These data support a role of MMP12 in promoting early repair processes following corneal epithelial injury by enhancing epithelial cell migration and neutrophil infiltration.
角膜上皮缺损是眼部发病的常见原因，如果不能正常愈合，可能会导致角膜瘢痕形成。基质金属蛋白酶（MMPs）是调节角膜修复多个方面的细胞外基质蛋白酶。我们之前已经表明，在涉及角膜全层损伤的化学损伤模型中，MMP12通过调节中性粒细胞和巨噬细胞浸润以及血管生成，对角膜纤维化具有保护作用。然而，MMP12在仅限于角膜上皮的损伤中的作用相对未知。本研究调查了MMP12在孤立性角膜上皮损伤后的修复作用。使用在野生型（WT）小鼠角膜上进行的角膜上皮清创损伤模型，我们发现Mmp12在角膜上皮损伤后早期表达，在损伤后8小时表达水平最高，在损伤后4天和8天表达水平较低。我们使用对WT和Mmp12小鼠进行的体内和体外划痕试验，研究了MMP12是否对上皮修复率和细胞迁移有影响。我们发现，MMP12的缺失导致体内和体外划痕伤口修复率降低。我们还发现，Mmp12小鼠的角膜在损伤后中性粒细胞浸润减少。然而，MMP12的缺失并不影响伤口中心的细胞增殖。这些数据支持MMP12通过增强上皮细胞迁移和中性粒细胞浸润，在促进角膜上皮损伤后的早期修复过程中发挥作用。
