The function of mast all Chymase to corneal disorders in vernal keratoconjunctivitis

我们测定了春季角结膜炎患者泪液中肥大细胞糜酶活性的水平。VKC患者泪液中有较高的凝乳酶活性。这些活性的程度与VKC的严重程度显著相关(r=0.9245，p&lt；0.001)。接下来，我们研究了糜酶对角膜上皮细胞的体外作用。凝乳酶引起阻滞素和纤维连接蛋白的蛋白分解，导致屏障功能降低，抑制角膜上皮细胞的迁移。此外，糜酶还可从角膜上皮细胞产生的细胞外基质中释放并激活转化生长因子-β_1。向角膜成纤维细胞释放转化生长因子-β_1转分化的角膜基质细胞。角膜肌成纤维细胞产生大量的干细胞因子。干细胞因子是一种重要的分子，在肥大细胞的增殖、成熟和趋化过程中起着至关重要的作用。我们推测存在一个正反馈环，在这个环中，凝乳酶通过转化生长因子-β_1将角质形成细胞分化为肌成纤维细胞，而肌成纤维细胞又通过SCF刺激肥大细胞。我们的研究发现，靶向凝乳酶可能会减轻VKC角膜并发症的严重程度。乳糜酶的特定抑制剂应该会在未来出现。

We determined the level of mast cell chymase activity in the tears of patients with vernal keratoconjunctivitis. High chymase activity was detected in the tear of VKC patients. The degree of these activity correlated significantly with VKC severity (r=0.9245, p<0.001).Next, we investigated the in vitro effects of chymase on corneal epithelial cells. Chymase caused the proteolysis of occludin and fibronectin, resulting in a decrease of barrier function and inhibition of migration of corneal epithelial cells. In addition, chymase released and activated TGF-β_1 from extracellular matrix produced by corneal epithelial cell. Released TGF-β_1 transdifferentiated keratocytes to corneal myofibroblasts. Corneal myofibroblasts produced a large amount of stem cell factor. Stem cell factor is an important molecule, which has a crucial role in proliferation, maturation and chemotaxis for mast cell. We speculate the existence of a positive feed-back loop in which chymase differentiate keratocyte to myofibroblasts via TGF-β_1 , and myofibroblasts in turn stimulate mast cell via SCF.The findings of our study that targeting chymase may lessen the severity of corneal complications in VKC. Specific inhibitors of chymase should become available in the future.